Low nephron number — resulting, for example, from prematurity or developmental anomalies — is a risk factor for the development of hypertension, chronic kidney disease and kidney failure. Considerable interest therefore exists in the mechanisms that regulate nephron endowment and contribute to the premature cessation of nephrogenesis following preterm birth. The cessation of nephrogenesis in utero or shortly after birth is synchronized across multiple niches in all mammals, and is coupled with the exhaustion of nephron progenitor cells. Consequently, no nephrons are formed after the cessation of developmental nephrogenesis, and lifelong renal function therefore depends on the complement of nephrons generated during gestation. In humans, a tenfold variation in nephron endowment between individuals contributes to differences in susceptibility to kidney disease; however, the mechanisms underlying this variation are not yet clear. Salient advances in our understanding of environmental inputs, and of intrinsic molecular mechanisms that contribute to the regulation of cessation timing or nephron progenitor cell exhaustion, have the potential to inform interventions to enhance nephron endowment and improve lifelong kidney health for susceptible individuals.