Although a nutritionally balanced, energy-controlled diet and regular exercise form the cornerstone of weight management, supporting therapies may include antiobesity medications when a clinician determines that pharmacologic assistance could contribute to treatment success. The US Food and Drug Administration has approved certain medications for helping achieve weight loss in patients with obesity or overweight who have comorbidities. However, some clinicians prescribe medications not approved for weight loss for this purpose. Evidence from clinical trials indicates that weight loss resulting from the use of many of these off-label pharmaceutical agents is modest, but in a range that correlates with favorable modification of cardiovascular risk factors, and significant when compared with placebo plus diet and lifestyle modification. Clinical trials also demonstrate a slight but significant effect in the weight-maintenance phases following weight loss. Pharmacotherapy alone, without behavior modification, is not effective; patients who respond to medication typically regain weight when the drug is discontinued. The fact that many weight-loss medications are sold over the Internet without a prescription suggests that they are being used without medical supervision. The purpose of this review is to present evidence for and against the obesity medications currently used in clinical practice, and the possible role for these agents in a person’s overall weight loss plan.