I actually received an amazing piece of advice when I was a rookie DM that helped me out a lot. This trick has never failed me, though you have to remember to use it sparingly or the players will start to resent it catch on.

Give them syphilis.

No, really. Hit them with some undesirable condition, and then let them find "clues" that imply that the only way to get rid of it is to [go to a certain place, do a certain thing, visit a certain person, whatever else you need them to do].

It does work, but don't abuse it.

~R~