Because multiple estrous cycles are required for heifers to express full fertility before first breeding, ensuring that puberty is achieved in advance of 14 mo of age is critical. This allows heifers to calve as 2 year olds and optimizes lifetime efficiency. Feeding diets that promote elevated BW gain during the prepubertal period has been the primary strategy for achieving these end-points. Based on research conducted in our laboratories and others, it appears that the interval between approximately 4 and 7 mo of age (juvenile period) is a critical window for metabolically programming the neuroendocrine axis to achieve targeted reproductive maturation in heifers. By focusing on nutritionally mediated changes in the hypothalamus, we have been able to characterize several structural and functional modifications in hypothalamic pathways that respond to high-energy diets during this period. These include the differential expression of several genes (NPY, AGRP, POMC, and GHR) within the arcuate nucleus, a reduction in NPY innervation of GnRH neurons, decreased concentrations of central NPY, and increased innervation of kisspeptin neurons by αMSH. These alterations are consistent with the hypothesis that accelerated growth during the juvenile period, resulting in increased circulating leptin, leads to decreased inhibition and accelerated excitation of GnRH neurons. Novel nutritional and managerial approaches for optimizing growth during sensitive periods of infantile and juvenile development are required in order for fundamental biology to reach practical translation. These approaches must facilitate nutritional imprinting of the brain during early calfhood, while minimizing feeding costs, optimizing the consistent establishment of estrous cycles by 11 to 12 mo of age, and avoiding precocious puberty or disrupted mammary gland development. Our recent studies indicate that this may be achieved by exposing heifers to a stair-step nutritional regimen. However, a role for the maternal metabolic environment in heifer offspring responses to postnatal diets may also be operative. If confirmed, successful managerial strategies will also include the pregnant dam (USDA-NIFA grants 2009-65203-05678 and 2013-67015-20960).