Out of the 21 quests in the game, 11 require the use (or discovery) of a special item in order to be completed. Probably the most involved of these is Khalim's Will, in Act 3. This quest will have you running around the jungle searching for a number of items that will then be placed in the always-handy Horadric Cube and transmuted along with a special flail to make another special flail (sounds fun).