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Bike shorts (yep, those sexy spandex ones!) can help, get good ones though, and you may need to try a few brands or models to see what works best. Just like on a bicycle, do not wear underwear underneath. And like your grandmother said, you need to change them and give them a chance to dry out, ideally should have more than 1 pair along on a trip... if it is bad, I'd suggest changing out of them often, and letting the wet pair dry (I'm talking about sweat here guys!)

A mountain bike racer I knew used to liberally dose his bike shorts with talcum/baby powder before putting them on, he said it helped with comfort. I have tried this (on bicycles) and haven't noticed any impact.

The best improvement for me was a Corbin seat.