The worldwide epidemic of obesity continues unabated. Obesity is notoriously difficult to treat, and, thus, prevention is critical. A new paradigm for prevention, which evolved from the notion that environmental factors in utero may influence lifelong health, has emerged in recent years. A large number of epidemiological studies have demonstrated a direct relationship between birth weight and BMI attained in later life. Although the data are limited by lack of information on potential confounders, these associations seem robust. Possible mechanisms include lasting changes in proportions of fat and lean body mass, central nervous system appetite control, and pancreatic structure and function. Additionally, lower birth weight seems to be associated with later risk for central obesity, which also confers increased cardiovascular risk. This association may be mediated through changes in the hypothalamic pituitary axis, insulin secretion and sensing, and vascular responsiveness. The combination of lower birth weight and higher attained BMI is most strongly associated with later disease risk. We are faced with the seeming paradox of increased adiposity at both ends of the birth weight spectrum-higher BMI with higher birth weight and increased central obesity with lower birth weight. Future research on molecular genetics, intrauterine growth, growth trajectories after birth, and relationships of fat and lean mass will elucidate relationships between early life experiences and later body proportions. Prevention of obesity starting in childhood is critical and can have lifelong, perhaps multigenerational, impact.