Objective: To assess the safety and efficacy of FDA-approved and in-development antiobesity agents. Data Sources: Literature was accessed through MEDLINE (1950-current) and EMBASE using the terms antiobesity agent, diethylpropion, phentermine, orlistat, topiramate, lorcaserin, bupropion, and naltrexone. In addition, reference citations from publications identified were reviewed. Files related to FDA expert panel hearings were retrieved from the FDA website. Study Selection and Data Extraction: Randomized double-blind trials assessing the efficacy and safety of antiobesity agents compared with placebo in the treatment of overweight and obese adults were reviewed. Only English-language or English-translated literature was reviewed. Medications were selected based on FDA approval status. Data Synthesis: Ten double-blind clinical trials were reviewed. There are currently 5 FDA-approved antiobesity agents and 1 agent recently rejected by the FDA. Study results for all agents showed statistically significant weight loss compared with placebo, but with varying adverse effects. The combination of phentermine and topiramate is the most efficacious antiobesity agent approved by the FDA. However, this combination has various neurologic, cardiovascular, and teratogenic safety risks that may limit its use. Based on its safety profile, orlistat is the preferred antiobesity medication, despite the lesser extent to which it induces weight loss versus newer agents. The incidence of unwanted gastrointestinal adverse effects limits its use. Conclusions: Despite a glaring medical need for options to treat obesity, available medications are limited. No current drug option is ideal; each has either safety risks or efficacy concerns. Safe agents that meet FDA efficacy standards are needed to help treat the obesity epidemic.