the effect rimonabant has on lipids will be additive to that of other agents, including statins. In patients with diabetes the reduction in HgbA1C seen with rimonabant 20 mg daily is once again no greater in magnitude than that seen with other available oral hypoglycemic agents; however, again the effect on other metabolic parameters appears to offer a unique beneﬁt in reducing cardiometabolic risk. Although all the efﬁcacy data currently available demon- strates considerable beneﬁt in a number of cardiometabolic parameters, determining the true magnitude of reduction in cardiometabolic risk will require long-term clinical trials (like STRADIVRIOUS) examining the effect on more clini- cally relevant endpoints than lipid parameters and levels of neurohormones. Of course, as with all pharmacological interventions, the demonstrable beneﬁt of rimonabant must be balanced against its safety and tolerability proﬁle. In the 6600 subjects in the RIO studies, rimonabant proved be generally safe and well tolerated. However, practitioners must keep in mind that this was a highly selected population carefully screened to exclude subjects who would be most prone to the psychiatric adverse events seen more commonly with rimonabant than with placebo. Given the high prevalence of mood and other psychiatric disorders among overweight and obese patients, pending further trials practitioners will need to be especially vigilant in screening for symptoms of depression before ini- tiation of and during treatment with rimonabant. One ﬁnal potential limitation of rimonabant as a useful clinical tool was also seen in RIO-NA where patients who discontinued rimonabant for the second year of the trial had substantial weight regain and reversal of previous improvements in lipid parameters. As such, it appears that treatment for well past 1 year may be needed to achieve sustainable reductions in cardiometabolic risk. In sum, based on its unique mechanism of action, rea- sonable safety and tolerability proﬁle, and the beneﬁcial improvements in weight, waist circumference, HDL-C, tri- glycerides and other factors seen in the RIO trials, in patients who are not at risk for signiﬁcant depression rimonabant appears to be a potentially important therapeutic agent in helping reduce cardiometabolic risk in overweight and obese individuals, especially those with concomitant metabolic syn- drome or T2DM. Its overall clinical effectiveness in reducing the progression of surrogate measures of atherosclerosis and the incidence of T2DM and CV events remains to be determined, as does its incremental beneﬁt when added to other risk reduction strategies and its position in our current treatment paradigms. 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