Although physiological deterioration occurs with advancing adult age, the interpretation of cross-sectional and longitudinal studies of age-changes in physiological processes are often complicated by confounders unrelated to aging. Age-associated disease is a major cause of physiological deterioration. To avoid this factor, only subjects free of discernible disease are used in many studies of what is referred to as “normal” aging. However, it is important to recognize that age-associated disease is not only a common occurrence but also an integral part of aging. Increasingly, gene-environment interactions are recognized as playing a major role in age-associated physiological deterioration, and there is great individual variation in both the rate of aging and the occurrence of age-associated physiological deterioration.