Dietary restriction (DR) has been shown to benefit health and longevity in a wide variety of species, although most have maximal life spans of only a few years. In 1987, the National Institute on Aging began the first well-controlled long-term study in a species with a considerably longer life span and a closer physiology to humans. Using rhesus monkeys (Macaca mulatta), an extensive array of physiological measures have been conducted in both males and females to evaluate the effects of DR. Monkeys benefit from DR with a lower body weight, body fat, blood glucose and thus are at lower risk for developing diabetes. Changes in several endocrine measures indicate an altered hormonal axis; however, circadian patterns and timing relative to the onset of DR can obscure the differences. Despite the caloric deficit, female monkeys are not reproductively compromised, and both males and females may benefit immunologically. There remains much to be learned from this model of DR including whether long-term DR will increase life span in a primate species.