In a Rock Band, the Lead Guitar is the part that you're hearing every time you hear one of those crazy mad solos. This guitarist is designated to the parts of the song that are compliment to the rhythm guitar's portion -- usually the fills, riffs, licks, and solos.
Good lead guitarists are fast with their fingers, know a lot about musical scales and, especially in jazz styles, good at improvisation (though this is not as critical in general rock styles, as solos in those types of songs are usually written beforehand, and not made up on the spot).
Of course, these are also the guys that know how to rock and make the ladies swoon, which is supposedly the reason a lot of high school kiddies pick up guitars in the first place.