Prior investigations suggested that treatment with the selective cannabinoid-1 receptor blocker rimonabant reduces body weight and improves several cardiometabolic risk factors. Pi-Sunyer and colleaguesArticle report results of a randomized trial comparing the efficacy and safety of rimonabant (5 mg and 20 mg) with placebo, plus diet and exercise, on 1- and 2-year changes in body weight and cardiometabolic risk factors in overweight or obese patients. The authors found that rimonabant was generally well tolerated and that the 20-mg dose was more effective than placebo in reducing weight, waist circumference, and triglyceride levels and increasing high-density lipoprotein cholesterol during the first year. In year 2, patients who continued taking 20 mg of rimonabant maintained their weight loss, whereas patients who were rerandomized to placebo regained weight. In an editorial, Simons-Morton and colleaguesArticle discuss the implications of participants' nonadherence and loss to follow-up for interpretation of the study results.