Insulin is an important regulator of glucose, lipid, and protein metabolism. It suppresses hepatic glucose and triglyceride production, inhibits adipose tissue lipolysis and whole-body and muscle proteolysis, and stimulates glucose uptake in muscle. In this review we discuss what is currently known about the control of substrate metabolism by insulin in men and women. The data available so far indicate that women are more sensitive to insulin with regards to glucose metabolism (both in the liver and in muscle), whereas there are no differences between men and women in insulin action on lipolysis. Potential differences exist in the regulation of plasma triglyceride concentration and protein metabolism by insulin and in changes in insulin action in response to stimuli (e.g., weight loss and exercise) that are known to alter insulin sensitivity. However, these areas have not been studied comprehensively enough to draw firm conclusions.