When Lana is attacked by her obsessed school pal Jake Pollan in the deserted swimming pool of Smallville High School, he is mortally shot by an unknown shooter. Meanwhile, Lex Luthor joins Luthor Corp. and his father, Lionel, requires a $50 million life insurance from him which increases Lex's suspicions. Clark investigates the murder of Jake, and finds that the criminal is Jake's friend Van McNulty, who is killing people affected by the meteor rock radiation, and Lex is the next in his death list. When Clark saves Lex, Van sees that he is special and includes Clark in his bill, and learning of his vulnerability, the growingly paranoid and racist Van concocts and shoots Clark with a kryptonite bullet, and then decides to go after Lana for her association with Clark. Also, Chloe discovers that Lionel has taken all her research documents of Clark after discovering that she has begun investigating Lex.

Lex is committed to the Belle Reve Sanitarium for the criminally insane by Lionel who forces the shrink, Dr. Claire Foster, to submit Lex to an experimental electroshock therapy technique to erase his memory and forget his past events. Clark visits Lex and after finding out, decides to try to save his friend, despite protests from Jonathan and Martha that Clark's secret is known by Lex. But three of Clark's adversaries reside in Belle Reve. They are the arrogant, power-stealing Eric Summers (from episode "Leech"), the angry, meteor-rock mutant racist Van McNulty (from episode "Extinction") and the double-clone Ian Randall (from episode "Dichotic") who join forces to attack him so Eric can steal Clark's powers again and and escape from the asylum. Meanwhile, Lana begins to distance herself from Clark while she's attending physical therapy to recover from her broken leg with the support of a charming patient named Adam Knight (Ian Somerhalder).