This chapter presents the history of the historical development of vertebrate models. The National Institute on Aging (NIA) has played a pivotal role in the development of animal models for aging. NIA decided to provide only specific pathogen-free (SPF) animals even though this meant that animals coming from the NIA facility would likely get sick upon arrival in a grantee facility that had an intercurrent disease problem. The Search for Biomarkers of Aging together with the National Center for Toxicological Research (NCTR) established in 1987 colonies of mice and rats to be used in a 10-year, 18-laboratory effort to develop biomarkers of aging that could eventually be used to test interventions in humans. The Senescence Accelerated Mouse (SAM) strains of mice were developed by Toshio Takeda at the Chest Disease Research Institute, Kyoto University, as the result of an accidental outcrossing of AKR/J mice and another unknown albino mouse strain in 1968. The most serious and systematic researches of nonhuman primate aging have developed as a consequence of an attempt to determine whether caloric restriction extends life and prevents disease in primates as it does in laboratory rodents. © 2006 Elsevier Inc. All rights reserved.