G protein coupled receptors provide attractive targets for drug therapy due to the sheer size and diversity of ligands within this receptor family. G protein-coupled receptor 40 (GPR40) functions as a cell-surface receptor for long-chain free fatty acids (FFAs). FFAs provide an important energy source, but also function as signaling molecules in various pathways, notably the process of insulin secretion. In pancreatic tissue, the interaction of long chain FFAs with GPR40 amplifies glucose-stimulated insulin secretion from beta cells, suggesting a possible role for GPR40 in the treatment of diabetes associated with insulin-deficiency. Specifically, the Arg211His polymorphism in the GPR40 gene may contribute to the variation of insulin secretory capacity in Japanese men. Also, GPR40 may be involved in the control of breast cancer cell growth by fatty acids and, therefore, provide a link between fat and cancer.