The extent to which common variants contribute to common phenotypes and disease in humans has important consequences for the future of medical genomics. Two reports have recently clarified this issue for one of the most pressing public health concerns, obesity. These large and comprehensive genome-wide association studies find that common variants within at least 11 genes are associated with obesity. Interestingly, most of these genes are highly expressed in the central nervous system, further highlighting its role in the pathogenesis of obesity. However, the individual and combined effects of these variants explain only a small fraction of the inherited variability in obesity, suggesting that rare variants may contribute significantly to the genetic predisposition for this condition.