Glucose intolerance is a nearly universal finding in patients with chronic renal failure and in animal models of uremia. The glucose intolerance results from impaired insulin-mediated glucose disposal by muscle, adipose, and liver tissue. Insulin binding by these tissues is not reduced. Rather, several defects exist in the postreceptor cascade of insulin action. Although impaired insulin-mediated glucose uptake and metabolism occur, the primary defect and causative agent are not established. The purpose of the present article is to review recent literature on the potential mechanisms underlying the insulin resistance of chronic renal failure.