It depends on where you start from, in terms of technique, I guess.
The main difference is in the palm-muting technique (not just when playing chords, but also when muting unused strings while playing lead).
You may have to adjust the position of your hand on the bridge a bit to catch all strings, and you may have to apply a bit more force to dampen them properly. Especially the low B is very sensitive, because it's so thick and under such low tension.
I'm still very new to it myself, but I think I got the hang of it after only a few hours of playing. I still make the occasional technical flaw, but I guess I can get away with that.
I've been playing for about 13 years on 6-strings btw, mostly playing lead in the style of Van Halen, Satriani, Vai, Petrucci and that lot... To get an idea of where I was coming from (or you could check my 6-string work on my soundclick page