Lana Lang is Clark Kent's first love and Lex Luthor's ex-wife. She founded the Isis Foundation, a non-profit devoted to helping meteor-infected metahumans, and also led the renovation of the Talon coffee shop.

Lana lived a mile away from the Kents and was admired from afar by her neighbor Clark Kent for years.

When they reached high school, Clark gained the courage to get to know her and she became an important part in his circle of friends. Clark and Lana have attempted to have a relationship several times, but for a long time he was unwilling to trust her with the secret of his true origins.

However, Lana knew Clark was hiding something, and to her mind this unspoken fact had always driven a wedge between them and prevented them from being together. Lana's relationship and subsequent marriage to Clark's former best friend Lex Luthor caused the breakdown of their friendship as well, even as Lana grew increasingly closer to finding out Clark's secret. After she faked her death to get out of her marriage, she later returned to Smallville. She and Clark reunited and she moved onto the farm to live with him and his cousin Kara.

Lana fell victim to evil Kryptonian computer Brainiac in his attempts to control Clark and Kara and was in a strange catatonic state for weeks. Lana awoke after Clark destroyed Brainiac; she broke up with him and has since moved away from Smallville. Lana, later, returned to Smallville for Chloe and Jimmy's wedding after training in not feeling pain and torture and has been stealing vital information from Lex. She successfully was fused with Project Prometheus. When Lex Luthor had Winslow Schott put a kryptonite bomb on the roof of the Daily Planet, Lana was forced to absorb the kryptonite. This infected Lana with kryptonite and therefore, Lana can no longer be near Clark. Lana left Smallville to use her abilities for good.