The risk of developing many adult-onset diseases, including hypertension, type 2 diabetes, and renal disease, is increased in low-birth-weight individuals. A potential underlying mechanism contributing to the onset of these diseases is the formation of a low nephron endowment during development. Evidence from the human, as well as many experimental animal models, has shown a strong association between low birth weight and a reduced nephron endowment. However, other animal models, particularly those in which the mother is exposed to elevated glucocorticoids for a short period, have shown a 20–40% reduction in nephron endowment without discernible changes in the birth weight of offspring. Such findings emphasize that a low birth weight is one, but certainly not the only, predictor of nephron endowment and suggests reduced nephron endowment and risk of developing adult-onset disease, even among normal-birth-weight individuals. Recognition of the dissociation between birth weight and nephron endowment is important for future studies aimed at elucidating the role of a reduced nephron endowment in the developmental programming of adult disease.