The recent discovery of widely distributed targeting determinants, which govern the polarized cell-surface distribution of plasma membrane proteins in epithelial cells, has significantly changed our view of how polarized cells generate functionally distinct membrane domains. Together with the surprising finding that the same determinants are recognized on both the biosynthetic and the endocytic pathways, it now appears likely that a common epigenetic code may exist that controls molecular sorting of membrane proteins in a wide variety of polarized, and perhaps even non-polarized, cell types.