Administration of exogenous insulin can ameliorate metabolic abnormalities in type II diabetes: It compensates for reduced endogenous insulin secretion, reduces excessive hepatic glucose production, and stimulates glucose uptake, enhancing both glucose oxidation and storage in the muscle tissue. In addition, insulin therapy has anti-atherogenic effects on serum lipid profile. The main concerns of insulin therapy are weight gain, hyperinsulinemia, hypoglycemia, and possibly sodium and fluid retention. Although studies in vitro and in experimental animals suggest that hyperinsulinemia may accelerate atherosclerosis, these data are not substantiated in patients with type II diabetes. Insulin therapy in type II diabetes patients can be used either temporarily when insulin requirements are increased (e.g., surgery, infection, pregnancy), or in the long-term when endogenous insulin secretion is vanishing or hyperglycemia does not respond to other therapy. Whether insulin should be used as a primary therapy in addition to diet and exercise in some patients has not been examined. The decision regarding the beginning of insulin therapy and targets should be established individually, taking into account factors such as age, other diseases, or life expectancy. Various regimens can be used, including evening insulin alone or in combination with oral agents, multiple injections, use of premixed insulins (short-plus intermediate-acting insulin in various combinations). Continuous subcutaneous insulin infusion also has been used. Comparative data between the regimens are scant, but a few studies suggest that no major differences occur between the regimens, with regard to glycemic control or hypoglycemic complications. In the future, insulin therapy in type II diabetes may become more common, particularly among patients with the autoimmune type of the disease.