A constant abundance of food and a sedentary lifestyle has led to an increasing prevalence of obesity in the United Kingdom. This has resulted in a serious public health problem as obesity, in particular the presence of excess abdominal (visceral) fat, is associated with a high risk of cardiovascular disease, type 2 diabetes and the metabolic syndrome. Managing obesity by lifestyle changes alone has met with only limited success, so pharmacological intervention is often necessary to help patients reduce their cardiometabolic risk profile. The recent discovery of the role of the CB1 receptors of the endocannabinoid system, and how these receptors influence appetite and energy storage, has led to the development of promising new approaches to the management of obesity. This review charts the background to the development of novel antagonists (CB1 blockers) directed against the CB1 receptors and briefly summarises the available phase III data. The available phase III data suggest that CB1 blockers could have a major role to play in the management of multiple cardiovascular risk factors, by reducing visceral fat and directly improving lipid and glucose metabolism and insulin resistance.