Regulation of intracellular protein trafficking is one of the central issues in cell biology. Extracellular proteins are delivered to cells via endocytosis. Many intracellular proteins are initially synthesized within the cytoplasm and cotranslationally inserted into the endoplasmic reticulum prior to being either sorted to their respective compartments or secreted. The pathways, regulation, and molecular signals involved in these processes are the subject of the present review. Individual sections focus on receptormediated endocytosis, coated pits, coated vesicles and clathrin, itinerary of endocytosed ligand, itinerary of endocytosed receptor, molecular signals in receptor structure, endocytotic sorting structures, role of Golgi and TGR, regulation of en dosoma I pH, transport of membrane compartments, vesicle transport systems, and proteolytic systems.