Prescription drugs have been available as weight loss aids in the United States for more than a century. Many different modes of action have been tried to effect weight loss. Most of the drugs require the patient to also initiate a low-calorie diet while on the medication. Mechanisms of action include centrally acting compounds that affect brain centers involved in mood, satiety, and hunger. Others act within the gastrointestinal tract to block fat absorption. Recently, use of several weight loss drugs has been associated with increased risk and adverse cardiovascular events, resulting in the removal of 1 approved drug from the market and the rejection of another compound from the Food and Drug Administration approval process. Nevertheless, the Food and Drug Administration did approve 2 new centrally acting drugs in 2012. Thus, today, there are a few new prescription drug choices for the physician treating an obese patient.