Many G-protein-coupled receptors (GPCRs) are regulated by endocytosis. Pharmacological studies defining distinct processes of ligand-induced sequestration and down-regulation provided early evidence for significant complexity in the endocytic membrane trafficking of GPCRs. In this review, we discuss our present understanding of the diversity and specificity of GPCR endocytic membrane trafficking, focusing primarily on proteolytic down-regulation of GPCRs via delivery to lysosomes. We discuss evidence suggesting that certain GPCRs can be targeted selectively to lysosomes after endocytosis by the same membrane pathway that mediates the process of rapid sequestration, and we highlight recent progress in understanding a mechanism that controls the sorting of a specific GPCR between distinct membrane pathways after endocytosis by clathrin-coated pits.