Obesity is quickly becoming the leading preventable cause of death in the USA. Over 60 obesity-related comorbidities exist which increase the complexity and cost of medical care in obese patients. Even a moderate weight loss of 5 % can reduce morbidity associated with these conditions. Lifestyle modification through caloric restriction and enhanced exercise and physical activity remain the first line treatment for obesity. The development of pharmacologic agents for the treatment of obesity has been challenged by both lack of efficacy and serious adverse side effects leading to their removal from market. Two new agents were recently approved by the US Food and Drug Administration to complement lifestyle modification in obese (BMI ≥30 kg/m(2)) and overweight patients (BMI ≥27 kg/m(2) and one obesity-related comorbidity). Lorcaserin is a novel serotonin 5-HT2C selective agonist which has been shown in three phase III studies to significantly reduce weight and cardiovascular risk factors such as diabetes. Phentermine/topiramate extended release (ER) is a novel combination of two agents which have individually been shown to significantly reduce weight. The combination agent phentermine/topiramate ER has been shown to reduce weight in overweight and obese subjects in a number of studies. This article reviews the pharmacology, clinical efficacy, and safety of these new agents compared to past and other presently available medications for the treatment of obesity.