This song is about a boy who is just ready to explode at his girlfriend, but she reasons him into calming down and getting along. He has tried to turn his back on her, but he can't. This song highlights the fallacies humans often share, especially with regard to taking life way too seriously. This is supported in the title itself, saying you only live once, so why dwell on all your problems and put yourself into a depression, especially when most of the time they are not even that important in the long run as you make it sound at the time.
This is the opening track on First Impressions Of Earth. An early version of the song entitled "I'll Try Anything Once" was included on the B-side for their "Heart In A Cage" single.
When this song was released as a single, The Strokes launched "Operation YOLO" (You Only Live Once), inviting all of their fans to call their local radio stations and request the song. The goal of this was to get a single played or requested the most just by word of mouth.
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