After a thirteen-year hiatus, the FDA approved two new anti-obesity drugs in 2012, lorcaserin (brand-name Belviq®) and a fixed-combination of topiramide and phentermine (brand-name Qsymia®); one new anti-obesity drug was approved in 2014, a fixed-combination of naltrexone and bupropion (brand-name Contrave®), and in 2015 the “high dose” liraglutide (brand-name Saxenda®) was approved for weight loss. During this time, the marketed anti-obesity drug sibutramine was withdrawn due to increase in non-fatal myocardial infarction and stroke incidence , two drugs targeting cannabinoid receptors were not approvable in the United States and the European Union due to concerns regarding suicidality and leptin at pharmacologic doses was not marketed due to disappointing efficacy. All approved drugs, in conjunction with diet and exercise, achieve more weight gain as compared to placebo. Efficacy between different drugs cannot be directly compared since no head-to-head studies have been performed; however, some drugs/drug combinations appear to provide substantially bigger reductions in weight than others or the respective monotherapies. Cardiovascular parameters, especially systolic blood pressure, triglycerides and HDL-cholesterol respond positively to even small amounts of weight loss; the same holds true for insulin and insulin resistance. Uric acid, an emerging risk factor for type 2 diabetes and cardiovascular disease, also tends to improve in response to weight loss although there is an increased short-term risk of gout. All drugs have specific side effects and several drugs do have black-box warnings; for example, for female patients, pregnancy needs to be ruled-out before starting topiramate and a negative pregnancy test is required every 4 weeks while on treatment with Qsymia, and buproprion needs to be tapered off slowly and not discontinued abruptly to decrease the risk of seizures. Treating overweight/obese subjects presents an opportunity and a challenge to physicians and patients. To achieve optimal weight loss with least complications, patients need to work on hypocaloric diets and exercise and physicians need to know the prescribing information of the prescribed weight-loss drugs.