It has been hypothesized that a reduced number of nephrons at birth contributes to the development of essential hypertension. Nephron number in normal human kidneys has been shown to vary up to eightfold. Therefore, a significant proportion of the population appears to be at risk for developing hypertension. Furthermore, nephron deficits might explain why some racial groups have a higher incidence of hypertension and end-stage renal disease than others. Animal studies have demonstrated that maternal limitations in nutrient supply, both gross and nutrient-specific; exposure to elevated levels of hormones or toxins; and genetic factors can lead to permanent deficits in nephron number and, when examined, elevated blood pressure. In this review, maternal and genetic factors influencing nephron endowment and the implications of nephron deficit for hypertension and renal disease in humans are discussed.