Obesity, particularly central obesity, is associated with insulin resistance. Much research has focused on mechanisms that link obesity to insulin resistance, including lipid accumulation in muscle and liver and the recently discovered adipocytokines. Insulin resistance is an important feature of a number of common conditions, including type 2 diabetes and polycystic ovary syndrome and is associated with rarer disorders, such as inherited insulin receptoropathies and genetic and acquired lipodystrophies. Despite its use for a number of years, metformin's role as an insulin sensitizer has only recently been appreciated. The discovery of a new class of insulin sensitizing agents, the thiazolidinediones, represents a major advance in the understanding of the etiology of insulin resistance, particularly in relation to adipocyte biology and possibly, its inflammatory origins.