This chapter reviews the current status of research into the notion that the current epidemic of non-communicable disease, particularly adult cardiovascular disease (CVD), originates during early development. It describes the potential of animals as models of human fetal development and presents the evidence from human and animal studies. The fetus offers the potential for detection of an individual's risk of disease even earlier in life, and may provide future early routes for intervention. However, in light of the ethical restrictions on human fetal investigations, suitable animal model alternatives are crucial in advancing this area of research. There is now considerable human and animal evidence to suggest that risk of later CVD is initiated by fetal phenotypic changes in response to a suboptimal intrauterine environment. Such prenatal adaptive responses may start as a response which is made to enhance immediate fetal survival or to optimize phenotype for the predicted later environment.