Eukaryotic cells have systems of internal organelles to synthesize lipids and membrane proteins, to release secreted proteins, to take up nutrients and to degrade membrane-bound and internalized molecules. Proteins and lipids move from organelle to organelle using transport vesicles. The accuracy of this traffic depends upon organelles being correctly recognized. In general, organelles are identified by the activated GTPases and specific lipid species that they display. These short-lived determinants provide organelles with an identity that is both unique and flexible. Recent studies have helped to establish how cells maintain and restrict these determinants and explain how this system is exploited by invading pathogens.