Obesity is a major health problem. The long–term success rate is low of diet and physical activity. Therefore, antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life–threatening disease, these drugs are required to be safe. Drugs developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn

. • Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves.

• Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010.

• Rimonabant was withdrawn because of significant psychiatric adverse effects.

• Orlistat was approved for long–term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects.

• Phentermine and diethylpropion can only be used for less than 12 weeks because the long–term safety of these drugs is unknown.

• Ephedrine and caffeine are natural substances but the effects on weight reduction are modest.

• Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long–term safety data are lacking. (Ther Adv in Drug Safe 2013;4(4):171–181)