Sheldon's fraternal twin sister, Missy, visits him. Immediately, Howard, Raj, and Leonard all find her attractive and try to woo her. Upon her greeting him, Raj decides to participate in a study to overcome social anxiety.
At Leonard and Sheldon's place, Howard and Leonard are both trying their best to impress Missy. Thanks to the help of a new drug, Raj shows up and joins the gang. Penny comes to Missy's rescue, inviting her to get their nails done.
Leonard confronts Sheldon privately to tell him that as Missy's brother, it's his job to protect the genetic integrity of her future offspring by helping Missy pick a suitable boyfriend. Sheldon quickly rules out all of his friends as potential mates, but Missy catches him in the act. She and Sheldon have a conversation of their own, after which Sheldon promptly lets his friends know that Missy can date whomever she chooses.
A Wii boxing match determines the outcome of which guy can ask Missy out: Leonard wins the match, but is refused by Missy. Howard tries his hand next, and fails, even with the aid of a few magic tricks. Though Missy is happy to see Raj at her door, it is at that time that his new drug wears off, so he is rendered speechless in the face of asking for a date.