Copyright: © 2012 Lacreuse A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Biomedical research often turns to nonhuman primates to answer crucial questions about the causes of a human disorder or the effectiveness of a specific treatment. Though primate research is currently enduring unprecedented criticisms, it has led to key advances in a number of areas important for public health. One of these areas is cognitive aging. In face of the markedly rising proportion of older people in the world [1], finding interventions to reduce cognitive aging has become one of the most important challenges of our time. Nonhuman primate (NHP) models of human cognitive aging are unique tools to develop and test new therapeutics against age-related cognitive decline. This editorial focuses on one promising -yet still highly debatedtherapy, hormonal replacement therapy (HRT). The concept behind the use of HRT to reduce cognitive aging is simple: As sex hormones decline with aging in both men and women, replacing these hormones may rejuvenate the cognitive abilities of the older individual. Once dubbed a “fountain of youth”, HRT quickly fell from grace following the publication of results of the Women’s Health Initiative study, which suggested that HRT may actually be harmful to older postmenopausal women, including for cognitive function [2]. In the context of the widespread negative press that ensued, and in spite of overwhelming evidence for positive effects of HRT on brain and cognition in animal models [3], HRT remains even today an uncertain avenue for menopausal women and older men. In this editorial, I briefly summarize the unique contribution of basic and translational research in NHP towards understanding the effects of HRT in the human brain.