As discussed elsewhere in this issue, beginning with David Barker’s insight and original observations leading to the Fetal Origins of Adult Disease hypothesis (1), epidemiologic studies have strongly suggested that an adverse intrauterine environment may lead to adult hypertension (2–5). However, not all reports have been able to document such an association (6), and the epidemiologic studies have been criticized on the basis that it may be impossible to account for all confounding variables (7). Moreover, human epidemiology does not provide cause–effect relationships. Therefore, experimental models serve two purposes. First, they should determine unequivocally, by eliminating the variation in genetic background and other risk factors, whether prenatal factors are capable of programming adult hypertension (“proof of principle”) and, if so, whether the characteristics of the hypertension are consistent with the experience in humans. Second, they are the key to unraveling the mechanisms involved. In this review, we discuss studies on animal models of prenatally programmed hypertension as they pertain to these two objectives. In the process, we incorporate published studies selectively to serve the goals of this discussion, and we apologize to the many investigators in the field whose work is not quoted.