You'll need to drop the crossmember and transmission plus remove the flexplate to replace the seal. If your truck is a 4x4, you'll have to drop the transfer case, too.
It's not technically complex work, but it is heavy grunt work. The worst part is getting at the top two bellhousing bolts-- it's really tight up there between the engine and firewall.
I had a warped flexplate that I replaced 2 years ago. I didn't replace the rear main at that time. However, a tooth chipped off last year from the new GM flexplate I installed-- arrggh. At least it wasn't due to a faulty installation, rather a hard starting problem.
Anyway, I farmed it out this time and had the mechanic replace it while he was in there. There's about 6 (?) retaining bolts that hold the seal housing in place. You'll need an impact wrench to get the flexplate bolts out. Ideally, you'd use fresh bolts when reinstalling the flexplate, too.
Again, it's not complicated but it's not necessarily easy, either.
Tools needed:
Jack stands
Tranny/floor jack
Impact wrench
Flexplate turner/wrench
Sockets
Torque wrench
Loctite
Here's the write-up I did on the flexplate replacement I performed:
http://www.geocities.com/kevinshorte.../Flxplate.html