Ligand binding to receptor tyrosine kinases and G‐protein‐coupled receptors initiates signal transduction events and induces receptor endocytosis via clathrin‐coated pits and vesicles. While receptor‐mediated endocytosis has been traditionally considered an effective mechanism to attenuate ligand‐activated responses, more recent studies demonstrate that signaling continues on the endocytic pathway. In fact, certain signaling events, such as the activation of the extracellular signal‐regulated kinases, appear to require endocytosis. Protein components of signal transduction cascades can assemble at clathrin coated pits and remain associated with endocytic vesicles following their dynamin‐dependent release from the plasma membrane. Thus, endocytic vesicles can function as a signaling compartment distinct from the plasma membrane. These observations demonstrate that endocytosis plays an important role in the activation and propagation of signaling pathways.