Obesity is epidemic; new medications and therapeutic options are urgently needed to reduce the associated health care burden. The initial clinical strategy for weight loss is lifestyle modification involving a combination of diet, exercise, and behavior change. However, it is difficult for many to achieve and maintain weight loss solely through this approach. Only two drugs, orlistat and sibutramine, have been approved by the US Food and Drug Administration (FDA) to treat obesity long term, and both medications have undesirable side effects, leaving an enormous unmet need for efficacious and safe therapy for obesity. Other medications with weight-loss effects have been approved by the FDA for short-term treatment of obesity or for disorders other than obesity, but these also have potential adverse effects. This article discusses the perceived benefits and risks of these approved medications along with emerging drugs that have shown weight-loss effects.