There is a lot of self-loathing going on in this song, as Kurt Cobain sings, "I'm so ugly" and takes the voice of a man on the brink of killing himself - dysfunctional, random, and all of that. Cobain made it clear that most of the time, he wasn't singing about himself in his songs, but was pulling from what he saw in other people. This depressive theme crept into some of the songs on their In Utero album as well, which at one point was going to be called "I Hate Myself And I Want To Die." At live shows, Cobain would sometimes put this in perspective, asking the audience, "Hey everybody, why so glum?"

Lithium is a drug used by doctors and psychiatrists to treat patients with manic-depressive disorder, also known as bipolar depression. This is a very volatile mental condition, and lithium often helps regulate the mood of the patient. Mike Tyson is a famous lithium patient.

The CD single contained a sonogram photo of Kurt Cobain and Courtney Love's unborn child, Frances Bean; Kurt said he thought he saw Frances doing the heavy metal devil horn hand gesture when he watched the sonogram. The single also included all the lyrics to the songs on the Nevermind album, so people could finally figure out what Kurt was singing in "Smells Like Teen Spirit."