Obesity is a growing worldwide epidemic that is associated with serious medical complications. Although diet and exercise are often effective treatment in the short run, the weight lost is usually regained unless intensive intervention is maintained. Pharmacological adjunctive measures are clearly needed, and topiramate is currently being investigated as a possible new therapy for obesity. This paper reviews three clinical trials of topiramate for weight reduction in obese subjects: a 6-month dose-ranging study, a 2-year study of weight loss, and a 44-week study in subjects who had previously lost weight on a low-calorie diet. All three studies found topiramate to be significantly more efficacious than placebo. Notably, weight loss continued for 1 year and, perhaps, could have continued for a longer period. Topiramate was generally well tolerated, with adverse events being mild to moderate and mostly related to the central nervous system. Paresthesia was a frequent occurrence, but it did not lead to withdrawal of >5% of the subjects in any study.