Binding of the peptide growth factors (GF) on their surface receptors triggers rapid endocytosis of ligand-receptor complexes via clathrin-coated pits. Internalized receptors pass through the endosomal compartment where they are efficiently sorted to the lysosomal degradation pathway. Accelerated internalization and degradation of GF receptors leads to dramatic down-regulation of the receptors. Hence, we discuss the pathways, molecular mechanisms and the biological role of the GF-induced receptor endocytosis and lysosomal targeting. The endocytosis of epidermal growth factor (EGF) receptor is employed as a model system to describe the role of clathrin, clathrin adaptors and other proteins in the recruitment of receptors into coated pits and in the endosomal sorting process.