Receptor tyrosine kinases of the insulin-insulin-like growth factor (IGF) family promote growth and mediate metabolic signals. Despite their extensive structural homology, genetic evidence indicates that their physiological functions are distinct. Nevertheless, there is limited evidence from cell culture systems suggesting that their signalling capabilities differ. Thus, it remains unclear whether the different physiological roles of insulin and IGF-I receptors result from intrinsic differences in their abilities to activate distinct signalling pathways, or arise from extrinsic differences, such as tissue distribution, relative abundance and developmental regulation.