Obesity is strongly associated with conditions such as hypertension, diabetes mellitus and osteoarthritis that have known adverse health outcomes. The rising prevalence of obesity threatens to overburden our health care system. As a result, the need for safe and effective treatment options is urgent. Unfortunately, pharmacologic treatment options have been disappointing either because of poor side effect profiles or limited long-term efficacy. Our goal is to review currently available pharmacologic treatments and the data supporting their use so that practicing physicians may better incorporate them into a comprehensive, long-term treatment strategy for their patients. We focus on orlistat and sibutramine as these are the two medicines approved by the FDA for long-term treatment of obesity. In addition, we review briefly agents approved for short-term use as well as agents such as zonisamide and topiramate which have shown some promise as weight loss agents in specific clinical circumstances. Finally, we highlight one medicine currently in phase III clinical trials, an endocannabinoid receptor antagonist. Given the overwhelming research focus on this disease, it is likely that the coming years will bring more treatment options, raising the chance that our patients will have meaningful and sustained weight loss.