According to the World Health Organization, obesity is a multifactorial disease with increasing frequency in many countries that can be characterized as an epidemic of major public health concern. Recognized since 1985 as a chronic disease, obesity is the second leading cause of preventable death, exceeded only by cigarette smoking. Obesity has been established as a major risk factor for diabetes, hypertension, cardiovascular disease and some cancers in both men and women. The general goals of obesity treatment are to reduce body weight, to maintain a lower body weight over the long term or to prevent further weight gain. Traditional methods to promote weight loss focus on reducing energy intake through low-calorie or low-fat diets, increasing energy expenditure by increase in physical activity, and behavioral modification. Numerous other weight loss interventions are available including pharmacotherapy, surgery to reduce food consumption and alternative therapies. Although the pharmacological treatment of obesity should not be the first therapeutic option, its use is now fully approved. Rimonabant is a selective cannabinoid-1 receptor antagonist that has been suggested to reduce hunger and consumption by affecting the endocannabinoid system. Rimonabant has entered the market in some countries as a promising new drug for obesity. However, although effective as an anti-obesity drug, rimonabant also causes serious adverse side-effects, thus is being doubted and denied for medical usage. This chapter focuses on the role of rimonabant as anti-obesity drug, elucidating the mechanisms of action, the main results of clinical trials, FDA and EMEA recommendations, and the future perspectives.