Watch the Highway Key online guitar lesson by Jeff McErlain from Essentials: Chord Tone Soloing
"Key to the Highway" is a consummate 8 bar blues. There are others, but this is the big kahuna. It's also a blues staple that I have heard people, such as myself, miss some golden opportunities in this song to utilize chord tone soloing. It still uses the same chords as a blues, just the order is mixed up little bit, but for some reason the song screams out for us to outline those changes more than a standard blues does. I think it's because the chords change so quickly, but I'm not sure.
There are some versions of the song by some very well-known guitar players where they don't make the changes at all. Eric Clapton is one of my favorite guitar players, especially during his John Mayall and Cream days. On the Derek and the Dominos record he plays the song and takes a solo. With all due respect, and I have a ton of it for him, he doesn't really make the changes so well.
In recent years, the song has become a staple in his set. At the time of writing this paragraph, I just saw him play last night, and he played the song and tore it up making the changes. It was a lesson in chord tone soloing and simplicity.