The present paper focuses on the different lines of evidence indicating that cannabinoid CB(1) receptor antagonists, including the prototype rimonabant, reduce food intake and body weight in laboratory animals. Recent clinical surveys demonstrated that rimonabant significantly reduced body weight also in overweight/obese humans. Treatment with rimonabant was associated with a beneficial effect on different metabolic parameters and cardiovascular risk factors linked to overweight. The data reviewed in this paper suggest that cannabinoid CB(1) receptor antagonists may constitute a novel class of drugs potentially effective in the treatment of obesity-related disorders.