Both epidemiological and clinical evidence suggest relationships between the antenatal environment and the risk of developing insulin resistance and associated cardiovascular disease (part of the metabolic syndrome) in middle age. However, interpretation of these findings has been controversial. Recent experimental observations provide considerable evidence for a causal model linking adaptive responses to early environmental cues and the later risk of disease. Evolutionary and life history theory provide possible explanations of why these phenomena have persisted and how they might cause disease. In this article, we review the clinical and experimental perspectives on the "developmental origins of disease" model in the context of these new concepts.