Modular domains that recognize and target intracellular membranes play a critical role in the assembly, localization, and function of signaling and trafficking complexes in eukaryotic cells. Large domain families, including PH, FYVE, PX, PHD, and C2 domains, combine specific, nonspecific, and multivalent interactions to achieve selective membrane targeting. Despite structural and functional diversity, general features of lipid recognition are evident in the various membrane-targeting mechanisms.