It was long believed that the effects of insulin are mediated by a unique insulin receptor. However, there is considerable evidence suggesting that insulin receptors in brain, liver, adipocytes, and lymphocytes are heterogeneous in structure and function. This evidence is based on comparisons of concentration response curves in cells and tissues, and on comparisons of binding and effects of insulin-derivatives and receptor antibodies. Two receptor isoforms (IR-A and IR-B) generated by alternative mRNA splicing have been identified, but cannot fully account for the observed differences in ligand binding and receptor function. It is suggested that the differences in ligand binding reflect yet to be defined post-translational modifications, and that post-receptor events are responsible for the observed heterogeneity of insulin action.