Monk notes to Trudy that they haven't been caroling since college. He thanks her for getting him out of the house and she asks about a missing woman, Wendy Stroud. Monk is heading down to the clinic where she worked to talk to her boss. He notices that something is wrong with Trudy and she says she has a lot to do and not enough time. Monk notices a present under the tree and Trudy asks him not to open it until Christmas because it's a surprise. They embrace and Trudy assures Monk that she loves him.
Later, Trudy goes down to the parking garage as a six-fingered man watches her. He finally approaches her and she runs for her car. She gets in and starts the engine… and the car explodes.
Monk and Stottlemeyer go to the midwife clinic and talk to Wendy's boss, Dr. Malcolm Nash, who says that he hasn't heard from Wendy. Stottlemeyer gets a call and is informed about Trudy's death, and he tells Monk the news.
Monk wakes up and finds Trudy sitting on his bed. She tells him he doesn't have to sleep just on his side of the bed and he insists he isn't sleeping by himself. Trudy tells him that it's time to say goodbye but Monk admits that he can't. She smiles and says it won't be much longer. Monk reaches for her hand… and she disappears.
Monk and Natalie are going to a new case and Natalie invites Monk to the dinner party she's having to introduce Julie to her boyfriend, Lt. Steven Albright. Monk tells Natalie what he dreamed and Natalie thinks it's an omen. They discover that the murder victim is Dr. Nash, who was killed at the same clinic Monk was at when he got the news about Trudy's death. Stottlemeyer explains that Nash was scanning in records when somebody snuck in and shot him twice in the head with a silenced pistol. While Monk goes over the scene, Disher talks about his two-week vacation to New York City but refuses to discuss specifics. Monk notices that all the pill bottles are there so the killer tried to make it appear as a robbery. He also determines that the killer used the computer and was left-handed.
Monk, Stottlemeyer, and the others go to see Judge Ethan Rickover to get a warrant. Ethan reviews the warrant and Stottlemeyer insists they have the right man. Ethan tells them that the governor wants him to join the State Supreme Court and they offer their congratulations.
The police search the suspect's apartment and talk to his ex-wife, Edie Kazarinski. She says that her ex-husband comes and goes as he pleases. Edie takes a photo of him out of the bird cage and shows it to him, while Monk notes that he gave Natalie the day off to be with her boyfriend.
Kazarinski gets a call and is informed there's a change of plans, and he left a partial fingerprint. The caller tells Kazarinski to eliminate Monk because he killed Trudy 12 years ago.
Trudy and Albright,are shopping for Monk as Kazarinski watches them. He approaches the cart with Monk's items and starts to walk away with it. Trudy stops him and he apologizes and then leaves.
That night, Natalie, Julie, and Lt. Albright have supper at Natalie's and they discuss Julie's future plans. She talks about how she'll be moving away, and Albright asks about the case. Monk starts choking briefly, and then starts cleaning spots. He realizes he's seeing spots and convulses, and they get him to the hospital. The nurse tries to take his blood but Monk is less than cooperative. She finally calls in over a dozen staff to hold him down. Dr. Matthew Shuler from the hematology department comes in and warns there is no good news. Monk has been deliberately poisoned with a synthetic toxin.
A hazmat team goes over Monk's apartment looking for the poison while Monk waits with the others for news. Shuler arrives and tells them that Monk was the only one affected, and they can't treat Monk until they identify the specific toxin. If they don't, Monk only has two or three days and will suffer from pain and vomiting before death. Natalie notices a newspaper with a photo of Kazarinski and realizes he was at the supermarket and briefly walked away with Monk's shopping cart. They prepare to go over everything she bought but Shuler warns there may not be enough time.
Stottlemeyer calls together a team of volunteer officers to investigate Nash, and try to and find Kazarinski. He warns them Kazarinski must be taken alive so they can determine what toxin he gave Monk.
At home, Monk is busy sorting the capsules in his medication. Meanwhile, Stottlemeyer confronts a suspect, Ronnie, who refuses to talk until Stottlemeyer hits him with Disher's laptop. The man reveals that Kazarinski bought a fake ID and a train ticket. Stottlemeyer sets up an undercover operation to watch for Kazarinski at the train station. Kazarinski, wearing a blonde wig, arrives and spots the police. Meanwhile, Disher says that he'll miss police work and notes he can't do it forever. Before Stottlemeyer can respond, he realizes that the announcer in the control tower has gone silent. Disher runs up there and discovers the man is dead. He calls Stottlemeyer, who warns him the microphone is still on. Disher fails to turn it off and sets off a panic as he warns that Kazarinski has taken the controller's uniform. Stottlemeyer spots Kazarinski and chases after him into the rail yard. The killer manages to elude Stottlemeyer but is hit by a passing train and is killed instantly.
Monk sees Dr. Bell and explains that they found chemicals in the dumpster at the hotel where Kazarinski was staying, but there's not enough time to come up with anything. All the food from the shopping cart turned up negative. Monk says that he has everything to be sorry about, that he's lived like a prisoner since Trudy's death and he hasn't accomplished anything if he hasn't solved his wife's murder. As Bell pencils in more appointments for Monk to try and reassure him, Monk gets up, tells him goodbye, and then leaves.
Disher reports to Stottlemeyer that the lab won't come up with anything in time. The captain pours out two drinks and explains that he always thought Monk wasn't human, but his friend saw and felt everything and was all too human.
Natalie drives Monk to the cemetery to say goodbye to Trudy. He simply says that he loves her and assures Natalie he can tell Trudy the rest tomorrow. Back at home, Natalie gets a call from Shuler, who insists Monk should go to the hospital. Monk insists on staying at his apartment and asks Natalie to get him the present Trudy had for him 12 years ago. She reluctantly gives it to him and he opens it to discover it's a video tape. On it, Trudy says that she had a secret, something terrible from before they met.