Body composition is reviewed as a composite of several traits each with their distinctive genetic basis, including major effects of genes at single loci. Studies involving twins, adopted offspring, and other family relatives have demonstrated the high heritability (0.4-0.7) of many of the traits involved. Genotype-environment interactions with diet and activity occur in domesticated animals and humans and associations with voluntary choice of diet and level of activity are unfavorable. Body composition is the main reference for a normal homeostatic mechanism involving appetite and energy expenditure control. Identification of major genes controlling products, such as leptin, indicate mechanisms for this control and its manifestations in leanness and obesity. The plasticity of certain aspects of body composition can be exploited by livestock breeders, although the side effects are unpredictable. They also promise the possibility of gene therapy in these hitherto intractable conditions. Novel major genes that are being rapidly uncovered in many species may enable future deployment of gene therapy. The control of body composition is likely to remain a challenge because of the unfavorable genetic correlations and the failure of ordinary, fallible humans to thwart the complex genetically programmed destiny they have inherited.