Accumulating evidence indicates that the insulin-like growth factors (IGFs) function not only as mitogenic factors, but also as promoters of cell motility. In this article we review the current knowledge concerning the biochemical mechanisms whereby the IGFs activate cell motility. A key aspect of IGF-stimulated cell motility is the ability of IGFs to promote actin polymerization at the leading edge of the cell. This effect of the IGFs is mediated by activation and autophosphorylation of the type I IGF receptor, followed by docking of insulin receptor substrate-1 (IRS-1), stimulation of phosphatidylinositol (PI) 3-kinase, and possibly activation of the small GTPase Rac. IGF-stimulated cell motility also requires the formation of new adhesions, a process associated with tyrosine phosphorylation of paxillin and focal adhesion kinase. Determining the biochemical mechanisms by which IGFs regulate cell motility should allow for a better understanding of bone remodeling, neurite outgrowth, tumor metastasis, placental formation, and skin and blood vessel repair. (c) 1997, Elsevier Science Inc. (Trends Endocrinol Metab 1997;8:1-6).