Obesity is a global problem that is predominantly caused by the increasing 
adoption of a low-cost, Westernised diet that is rich in fat and sugar and a 
more sedentary lifestyle. The costs of this epidemic are substantial increases 
in Type 2 diabetes, cardiovascular disease and some types of cancer that are 
certain to place a huge burden on individuals, healthcare providers and society. 
In this review, we provide an overview of the chequered history of 
pharmacotherapy for the treatment of obesity and an analysis of the regulatory 
and commercial challenges for developing new centrally-acting drugs in this 
metabolic indication. The efficacy and safety of the drug candidates that are 
currently at the pre-registration phase, i.e., lorcaserin, Qnexa and Contrave, 
are critically assessed. The main focus, however, is to provide a comprehensive 
review of the wide range of novel CNS compounds that are in the discovery phase 
or early clinical development. The profiles of various clinical candidates in 
animal models of obesity predict that several new CNS approaches in the clinic 
have the potential to deliver greater weight-loss than existing agents. This 
article is part of a Special Issue entitled 'Central Control of Food Intake'.