The drug itself, lithium, is typically used as a mood stabilizer to prevent acute manic behavior in patients with bipolar disorder. Lee chose the title as a "metaphor for happiness from a negative point of view": "It's looking at it like, 'I don't want to numb myself and not feel anymore'." She explained that during her process of writing music, she would get into a mood or a "strange low that I ride" that she would try to overcome by telling herself to let go of certain things, change and rejoice again; such experiences also inspired her to write "Lithium". Initially, Lee was indecisive as to which song to choose as the second single from "The Open Door", having in mind four different album tracks. "Lithium" was eventually chosen and made available for digital download on December 4, 2006. It was physically released in the United Kingdom on January 8, 2007. "The Last Song I'm Wasting on You", a track originally written for "The Open Door" and later included as a bonus track on several editions of the album, was the single's B-side.