Insulin-like growth factor-II (IGF-II) affects many aspects of cellular function through its ability to activate several different receptors and, consequently, numerous intracellular signalling molecules. Thus, IGF-II is a key regulator of normal foetal development and growth. However, abnormalities in IGF-II function are associated with cardiovascular disease and cancer. Here, we review the cellular mechanisms by which IGF-II's physiological and pathophysiological actions are exerted by discussing the involvement of the type 1 and type 2 IGF receptors (IGF1R and IGF2R), the insulin receptor and the downstream MAP kinase, PI-3 kinase and G-protein-coupled signalling pathways in mediating IGF-II stimulated cellular proliferation, survival, differentiation and migration. © 2011 Informa UK, Ltd.