The video features the band playing on top of the abandoned Linda Vista Community Hospital. 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. The music video was directed by Mark Pellington, best known for his work on the video for ' Jeremy' by Pearl Jam. During the first rehearsals, Grohl came close to injuring his throat and felt afraid of being unable to perform live, but eventually considered he could pull it off as 'when you go out and sing words from the heart, you scream twice as hard.” Music video It’s the fight in the face of adversity.' Grohl added that 'Most people think it's a love song but it's meant to be more universal, which I think is one of the reasons so many people sing along when we play it.' The composition had no interest in 'an interesting melody', instead featuring 'a rhythm that we'd never really used on any of the other albums.' The focus was on a strong performance, where Grohl could ' scream the whole way through'. It’s about the refusal to be taken advantage of by something that’s bigger than you, or someone you’re in love with.

Given the Kerry rallies inspired him to do 'all these songs about breaking away from the things that confine you', thus came 'a song of resistance. Grohl stated that while many of his songs start with the music and lyrics come last, the words for 'Best of You' were fast to write. 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'. It was only brought back for further production by manager John Silva, who felt 'Best of You''s absence while listening to what they had recorded that far.

Once the Foo Fighters recorded a demo, they shelved it feeling they could do better. 'Best Of You' was one of the first compositions for In Your Honor, written by Dave Grohl in his garage following his involvement on the campaign trail for John Kerry.

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