The role of genetics in obesity is twofold. Studying rare mutations in humans and model organisms provides fundamental insight into a complex physiological process, and complements population-based studies that seek to reveal primary causes. Remarkable progress has been made on both fronts, and the pace of advance is likely to accelerate as functional genomics and the human genome project expand and mature. Approaches based on mendelian and quantitative genetics may well converge, and lead ultimately to more rational and selective therapies.