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The present paper is reviewing the current place of weight-reducing drugs in the overall management of overweight/obese subjects, especially those with metabolic disorders and type 2 diabetes. Anti-obesity agents should be carefully evaluated in long-term (1-2 years) randomized controlled trials. Recent systematic reviews and meta-analysis assessed both the safety and efficacy of the two drugs currently used in the treatment of obesity, i.e. orlistat, a gastric and pancreatic lipase inhibitor that reduces fat absorption from the gut, and sibutramine, a combined norepinephrine and serotonin reuptake inhibitor that regulates food intake. Rimonabant, a new compound acting as selective blocker of CB1 receptors of the endocannabinoid system, raises much interest as it promotes weight reduction by a central effect and also exerts peripheral effects targeting cardiometabolic risk. Special attention will be paid to beneficial metabolic effects resulting from (even moderate) weight loss and to possible additional effects beyond weight reduction.