Although it is not generally a life-threatening disease, obesity is becoming a major health problem worldwide. It can be controlled by means of drugs, and, consequently, these are required to be safe as well as effective. In this paper, we summarize the fate of various drugs that have been introduced for clinical use in the treatment of obesity. Fenfluramine and dexfenfluramine were withdrawn because of heart valve damage. Sibutramine suppresses appetite and increases heart rate and blood pressure. In the Sibutramine Cardiovascular OUTcomes trial, an increase in major adverse cardiovascular events prompted its withdrawal in Europe and the United States. Rimonabant is an endocannabinoid receptor antagonist that reduces body weight and ameliorates some cardiovascular risk factors. However, adverse psychiatric side effects led to its withdrawal as well. Orlistat is approved in Europe and the United States for the treatment of obesity, but its use is limited by gastrointestinal side-effects. Ephedrine and caffeine are natural ingredients in foods and supplements that may help the person to lose weight. In the light of several failed attempts, there is a clear need to develop drugs that are effective and safe in the long term in order to successfully combat the phenomenon of obesity .