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).

Alicia Baker returns, and with the help of Red Kryptonite, elopes in Las Vegas with Clark. Lana offers a sexual relationship to Jason in an attempt to win him back. Lionel comes back to Lex with a peace offering.

Oliver Queen is poisoned at a charity fundraiser and Clark races around the world to find a cure.