The ability to sort proteins to different intracellular compartments is an essential property of all cells. Many diseases are caused by a failure of certain proteins to be sorted properly in the endocytic and secretory pathways. In addition, various intracellular pathogens use their hosts' protein-sorting machinery at different stages of their life cycles. These facts underscore the importance of understanding the mechanisms of protein sorting at a molecular level. In this article, we review recent advances in the identification of signals that direct proteins to their correct intracellular locations and of the recognition molecules that bind to the signals. The implications of these findings for the trafficking of various proteins are discussed.