Dave Grohl notes that the song was written following appearances at 2004 American presidential candidate John Kerry's campaign trail and is "about breaking away from the things that confine you".

In September 2023, for the 35th anniversary of Hot Modern Rock Tracks (which by then had been renamed to Alternative Airplay),[4] Billboard ranked "Best of You" at number 91 on its list of the 100 most successful songs in the chart's history.

[6] Taylor Hawkins declared that it was the only song from the rock disc of that album that remained from the original sessions along with "No Way Back".

He was inspired by the death of his wife a few months prior to the shoot, and was drawn to the song's notion of dealing with pain in life.

Along with the band's scenes are clips that show pain, depression, or anger: "Best of You" is widely regarded as one of the Foo Fighters' best songs.