Receptor-mediated endocytosis (RME) provides one major pathway for the trafficking of extracellular molecules into the cell. This involves the binding of a ligand to a specific cell surface receptor, clustering of the ligand-receptor complexes in coated pits, invagination and pinching off of the coated pits to form coated vesicles, and delivery of coated vesicles to discrete membrane-limited cytoplasmic sorting organelles, endosomes. Within these endosomes, ligands and receptors are each targeted to their appropriate cellular destination (e.g., lysosome, cytoplasm, opposite cell surface). The cell and molecular biologic basis for such a tightly regulated process is now beginning to be understood and is reviewed herein.