Peptide hormones and growth factors initiate signalling by binding to and activating their cell surface receptors. The activated receptors interact with and modulate the activity of cell surface enzymes and adaptor proteins which entrain a series of reactions leading to metabolic and proliferative signals. Rapid internalization of ligand-receptor complexes into the endosomal system both prolongs and augments events initiated at the cell surface. In addition endocytosis brings activated receptors into contact with a wider range of substrates giving rise to unique signalling events critical for modulating proliferation and apoptosis. Within the endosomal system, receptor function is regulated by lowering vacuolar pH, augmenting ligand proteolysis and promoting receptor kinase dephosphorylation. Ubiquitination-deubiquitination plays a key role in regulating receptor traffic through the endosomal system resulting in either recycling to the cell surface or degradation in multivesicular-lysosomal elements. From a clinical perspective there are several studies showing that manipulating endosomal processes may constitute a new therapeutic strategy.