The growing worldwide prevalence of obesity needs urgent attention because the potential morbidity, mortality, and economic tolls have to be avoided. Despite obesity is known as a healthcare issue on an epidemic scale, it remains largely an unsolved medical problem. The successful management of obesity is theoretically possible through lifestyle changes, with diet modifications and increasing physical activity. However, low results by traditional treatments have inevitably prompted interest in the development of effective therapies, including pharmacological interventions and gastrointestinal surgery. As our knowledge of the physiological systems regulating food intake and body weight has considerably increased over the past decade, many studies have underlined the scientific and clinical relevance of potential treatments based on peripheral hormones or central neuropeptides signals. Here we have summarized the complex pattern of the appetite regulation, divided into central and peripheral mechanisms. In the second part of this paper, we have reviewed the currently approved and putative obesity therapies. Up to now only two drugs, sibutramine and orlistat have been approved by the Food and Drug Administration for long term use, but several other medications are currently used to cure severe obesity and many other are developing. Thus, in the last part, we have analyzed recent literature and patents describing new and upcoming molecules. The new anti-obesity drugs under clinical development include agents affecting peripheral and central mechanisms. Further investigations are needed to approve these upcoming therapeutic agents for the treatment of obesity.