If you know the intervals of the song, 1, 4, 5, etc you can play the song in any key. This is roughly how the Nashville numbering system works.
I've been given songs to learn for a gig and been told, "Oh, didn't we tell you, we play this in E!" Usually changed to a key that is easiest for the guitarist to play! Finger positions you're familiar with go out the window and you have to rely on remembering patterns and intervals.