Eddie lies dying of lung cancer as his wife Charlotte looks on with his friends and relatives who have gathered to pay their final respects. Eddie asks to be alone with his wife and then apologizes for never taking her to Rio. Charlotte says she loves him and always has. Eddie says he's ready but then Charlotte starts to gasp for breath. She clutches at her throat as Eddie calls for help.
House arrives at his office and Taub gives him the case on Charlotte. House is more curious to learn why Thirteen and Kutner are missing. Kutner's dog is sick and Thirteen is with a patient. House is more interested in noting that Taub stole Kutner's cure for their previous patient. Charlotte did visit her sister in Hawaii, suggesting meliodosis, but it would have spread to Eddie. Taub suggests a virus and House orders treatment, but Thirteen arrives informs them that Charlotte is demanding to be released. The wife believes that Eddie got stronger when she stopped breathing. House agrees to send her home but Taub has an idea. He brings Eddie in to his wife's room.
House is seeing a young girl, Rosabel, in the clinic. She appears to be insensate but House realizes that she's been drinking her mother's mouthwash. The team informs House that Charlotte is recovering, but he isn't interested. Instead he wants to know where Kutner is. They're interrupted when Charlotte has another respiratory attack and Taub can't account for it.
Thirteen and Foreman go to Kutner's apartment but get no answer. They go in and they find… his corpse. Kutner has apparently shot himself in the head and is long dead.
The team meets and initially no one has anything to say. House finally wonders if Kutner said anything to anyone about any problems he was having. He wonders if Kutner panicked and starts to blame the team, and then admits he's just trying to figure out why he didn't reach out to any of them. Thirteen says Kutner didn't reach out to them but Foreman blames himself for not seeing anything suspicious. Taub insists Kutner was an idiot and would rather deal with their patients. He thinks Eddie is willing himself to live, but Foreman suggests they should pass it on to another doctor. House disagrees and says it'll never be okay. As House forces the team back to differential, Cuddy comes in to offer grief counseling and time off if they want it. The best they can come up with on Charlotte is polyserositis and House orders treatment. As he goes to his office, Cuddy trails along and House insists that he's fine. Wilson is absent for the moment, and Cuddy wonders if House knew anything House admits he didn't. Cuddy apologizes for his loss, but House insists it isn't his loss. Taub goes to treat Charlotte and House decides to go with Foreman and Thirteen to see Kutner's parents.
Taub explains the anti-inflammatory treatment to Charlotte while Eddie tells her to imagine that she finally made it down to Rio. Taub interrupts him to run one more test on Eddie.
Kutner's adoptive parents Julia and Richard show House and the others photos of Kutner and talk about his childhood. They ask if they had any idea why Kutner shot himself, and House suggests that Kutner lived in a divided world. He says Kutner's parents should have let him keep his original last name and they didn't understand him. Richard snaps at him but House continues, saying Kutner just buried his pain deeper. Foreman tells him to go back to the hospital. He offers his condolences and leaves.
Taub reports to House that Charlotte's treatment didn't take, but Eddie seems to be recovering. House notes that Taub didn't ask about Kutner, but Taub insists Kutner didn't want help. House concludes that Taub tried to kill himself, but Taub refuses to be distracted. House realizes that if none of the diagnoses fit, there's only one diagnosis left. He believes she has hypertrophic cardial myopothy, and they need to induce a massive heart attack to destroy the extreme muscle. He finally admits he's lying, to convince Charlotte to tell the truth. He explains that Charlotte is faking so that Eddie will hang on. Charlotte admits it's true and that they've become closer, but then clutches at her leg in pain. House checks her legs and discovers muscle dissipation proving that she's not faking.
House goes back over the case, and admits that he was wrong about Kutner having racial problems. Taub suggests MS and House orders a MRI to confirm, then tells Taub to do an echo on Eddie to see if he's improving. House confronts Cuddy and points out that Kutner had a public streaking record. Cuddy figures he's still deflecting and that Kutner was a lot like House, but House says if he thought that way then he would have realized it's better to live in misery than die.
Thirteen discusses Charlotte's 30-year relationship while running the MRI, and Charlotte admits that Eddie never showed much affection toward her even though he loved her. However, she didn't need him to. She passes out and Thirteen runs to her aid. Meanwhile, Taub runs the echo and Eddie hopes he has more time with Charlotte to do better by her. Taub is skeptical and says it's easier to think about it then to do it. He determines that Eddie's heart hasn't improved.
Cuddy goes to see Wilson and tells him that House needs him. Wilson thinks Cuddy just wants someone to take care of House, and she explains what House said to Kutner's parents.
Chase operates on Charlotte's spleen so they can biopsy it for rheumatic arthritis. He wonders why Taub is watching, and tells him to go home to mourn his friend. Taub insists he's more concerned about Charlotte who wanted to live. Chase determines that whatever Charlotte has is spreading to her liver.
House goes to Kutner's apartment and tries to find some clue to why he killed himself. Wilson arrives and wonders if his friend is okay. House that Kutner kept pictures of his birth parents and adoptive parents side by side, and had no reason to hide any other pain. Wilson suggests they go get drunk but House insists he's missing something. Wilson thinks he's trying to solve a puzzle, but House concludes that he didn't miss something and Kutner was murdered.
Back in differential, House informs Thirteen and Taub that Foreman took time off. Thirteen wasn't aware that her boyfriend took the time off. Taub admits that Eddie isn't improving, so House turns to Kutner's murder. He goes over possible motives and tells them to investigate, but Thirteen refuses to chase ghosts. Taub wonders why House is pursuing the irrational, and House turns back to Charlotte and tells them to test for an alpha 1 anti-trypsin deficiency. As Taub runs the test, Charlotte asks to be with Eddie. She asks about whether someone can bypass the organ donation registry, then tells Taub to transplant her heart into Eddie if she dies first.
Thirteen goes to see Foreman, who apologizes for wanting to deal with Kutner's suicide on her own like he's dealt with other bad things in his life. Upset, she turns and goes.
Cuddy discovers that House is going through Kutner's e-mails. He believes that the man who murdered Kutner's birth parents, and who is due to be released for parole. Cuddy doesn't believe it and House concludes she won't transfer Charlotte's case because it's the only thing holding him together. She promises to find him another patient if he'll cure Charlotte.
Charlotte goes into seizures but Taub realizes that she tried to kill herself so Eddie could have her heart. They stabilize her but her liver is destroyed and she only has 24 hours unless she gets a new liver. Taub insists she did it out of love but House doesn't believe it. They can't authorize a transplant without a diagnosis, but House is willing to lie. Taub says they should be honest and tell Cuddy the truth, just like Kutner would have suggested.
House decides to talk to Cameron, who realizes he want to think it's murder because it lets him off the hook. House suggests they get a partial liver transplant from Eddie, but she points out that would kill him. House admits it would, and Charlotte would get the whole liver. House believes Eddie would only do it if he loves Charlotte, and wanted to get Cameron's opinion. She explains it to Eddie, who agrees. Cameron warns that if they warn Charlotte by letting him say goodbye, it may tip her off. Eddie realizes his wife will resent her but signs the donation papers nonetheless.
Cameron points out to House that Eddie has nodules on his fingers, meaning he has something that could be curable. House doesn't believe her and Cameron wonders why. House has learned that the killer of Kutner's birth parents died two months ago. Cameron says he didn't get a chance to save Kutner, but he can run the tests and save Eddie.
After running the tests, House tells Eddie that he is suffering from cardiac blastomycosis brought on by a fungus infection. It's rare but curable, and his emotional state altered his body chemistry and put him into temporary remission. Eddie refuses the treatment, saying he was ready to die. He warns that if House won't do it, he'll go out after he's released and kill himself so they can take his liver then.
House explains the situation to Taub and Thirteen, saying if they agree to Eddie's demands they can protect the liver. Thirteen refuses to do it but Taub agrees, saying they've already had one pointless death. However, Taub takes Eddie to Charlotte and explains the situation, then asks her what she wants him to do. Charlotte passes out from fever as her white cells increase. Taub insists he did the right thing by convincing Eddie to live. Nothing fits the symptoms and House realizes that there's a clue they don't have. House goes to see Charlotte and demands answers: she realizes that Charlotte didn't go to Hawaii. She went to Rio, where she caught visceral leishmaniasis caused by sand flies. Charlotte admits that she went to Rio with a friend when she grew tired of waiting for Eddie to take her. House orders antimony treatment and has Cuddy find Charlotte a liver.
Later, Cuddy gets the liver shipped but Taub tells her the treatment isn't taking because they diagnosed her too late. She's leaving for Kutner's funeral with the others, but Taub refuses to go with her. She tries to console him, saying that Charlotte bought them time to save Eddie, but Taub doesn't think it gave her death any meaning.
Wilson confronts House, saying he is in pain. He's worried that House is terrified of losing his gift, and what he'll do if he accepts that. House tells him to go to the funeral.
Cuddy, Cameron, Chase, Wilson, Taub, and Thirteen attend the Hindu funeral with Kutner's friends and family. Thirteen sees Foreman in the back, watching. Thirteen and Foreman are among the pallbearers.
Eddie takes Charlotte's hand and kisses it as she dies. He and Taub watch as she passes away.
House goes back to Kutner's apartment and wonders what he's missed as he examines photos of his life.
Foreman takes Thirteen's hand.
Taub sits in the hospital corridor, alone and crying.