Ten years ago, 20 Rab proteins had been identified as organelle-specific GTPases, and two were known to be essential for vesicle targeting in yeast. Today, more than 60 mammalian Rab proteins have been identified. While Rabs were always viewed as key regulatory factors, no one could have anticipated their diversity of functions and multitude of effectors. Rabs organize distinct protein scaffolds within a single organelle and act in a combinatorial manner with their effectors to regulate all stages of membrane traffic.