The prevalences of overweightedness and obesity are increasing globally at frightening rates, driven by social and economic changes. Furthermore, obesity is associated with the pathogeneses of major diseases, particularly diabetes and cardiovascular diseases. However, no satisfactorily safe, effective obesity drugs are commercially available at the present time. Only two drugs have been approved in the United States for the long-term treatment of obesity, sibutramine and orlistat. However, these drugs are minimally effective and have significant side effects, which are likely inhibit their use. Therefore, there is a huge opportunity to make a significant impact on the lives of obese people through the discovery and development of additional pharmacotherapeutic options. In this review article, the authors focus on selected trends in medicinal chemistry and the approaches used to develop drugs for treating obesity.