As a method of losing weight and maintaining weight loss, calorie-restricted diets are proving ineffective and counterproductive. The best candidates for drug therapy for obesity include patients with comorbidities that can be decreased with weight loss and those at risk for obesity-related comorbidities. The central nervous system properties of the amphetamines have led to chemical alterations of the original molecule in the hope of creating an appetite-suppressant drug without the potential for abuse. Studies demonstrate that serotonergic drugs can induce weight loss in the short term. Patients using nonprescription drugs for weight loss that have not been approved for that purpose should be informed that efficacy is unproved and warned that, in some cases, adverse effects could be serious.