In general population, many protective immune responses are impaired in old age, leading to an increased risk of infection. However, recent studies in SENIEUR subjects (healthy centenarians who are examples of successful aging) suggest that complex remodeling and reshaping of the immune system occurs with aging. An appropriate regular regimen of endurance exercise might help elderly to lead a quality of life by preserving immune function. However, very little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many physiological systems which are known to alter the immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. The immune system response to exercise is multifaceted, depending on the nature of exercise. Significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in immune function are known to occur. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system by increasing the production of endocrine hormones which may contribute to less accumulation of autoreactive immune cells by enhancing the programmed cell death. Active elderly subjects demonstrated a significantly greater proliferative response to phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. A moderate training program can enhance the resting natural killer (NK) cell function of healthy elderly people, potentially increasing resistance to both viral infections and preventing the formation of malignant cells. Recent studies have suggested that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine production. It is important that the dose of physical activity needed to optimize immune function be defined more clearly at various points during the aging process both in females and males in order to optimize the immune function and to prevent any rise in adverse effects of exercise on the elderly population.