Insulin resistance is characterized by impaired responsiveness to endogenous or exogenous insulin. Loss of responsiveness is associated with a "clustering" of cardiovascular risk factors that includes abdominal obesity, hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia; this association is referred to as the insulin resistance syndrome (IRS). We searched MEDLINE, using the term insulin resistance, and reviewed relevant publications. We review the mechanisms and clinical consequences attributed to IRS, along with patient assessment and treatment options. It is possible to improve insulin sensitivity by caloric restriction, weight loss, exercise, and drug therapy. Metformin and troglitazone, approved for use in the treatment of type 2 diabetes mellitus (DM), improve insulin sensitivity and lower plasma glucose concentrations. Several other medications that may improve insulin sensitivity are currently under clinical investigation. Studies are needed to determine the effect of these medications on morbidity and mortality of patients with insulin resistance and type 2 DM.