The character of Sawyer was originally meant to be an older, slick, suit-wearing city con artist from Buffalo, NY. However, when Josh Holloway forgot a line at his audition and subsequently kicked a chair in frustration and loudly swore, the writers liked the edge he brought to the Sawyer character and decided to write Sawyer as more of a Southern, darker drifter instead.

Originally, Michael Keaton was cast as Jack. In the first draft of the script Jack was to be killed by the monster after they arrived at the cockpit. ABC told the producers that they shouldn't kill off the hero so soon in the series and the script was changed. After the change, Michael Keaton backed out of the role since he did not want to commit to a regular series.

Yunjin Kim originally read for the character of Kate. The producers felt she was not what they were looking for in Kate, but decided to create a new character for her, along with a spouse.

Originally, Michael Emerson was only cast for a few episodes in season two. The producers were so impressed with his performance that they cast him as a regular and rewrote his part to feature him more prominently.

After the character of Richard Alpert was first introduced on the show, a furious internet debate arose about whether or not Nestor Carbonell was wearing eyeliner onscreen. Carbonell revealed on the fifth season DVD extras that not only does he not wear eyeliner, mascara, or makeup of any kind to make his lashes and eyeline appear as dark as they do, but also the makeup artists for "Lost" actually use concealer on his lashes and under his eyes to try to tone down the natural darkness of his eyeline. He also said that the unusual appearance of his eyes caused him to get teased and bullied when he was a child. The writers, amused by the intensity of the debate, placed a reference to it in the series when Sawyer, who frequently applies nicknames to various characters, calls Alpert "eyeliner."