The disablement process is often accompanied by sarcopenia or muscle loss, which is associated with virtually all identified disability risk factors. Clinically, the association between body composition and physical performance has been documented by several studies. However, loss of strength is greater than loss of muscle mass with age implying that the quality of remaining muscle may be reduced. Although there are limited data explaining potential physiological mechanisms that contribute to muscle quality, sarcopenia is frequently associated with fat accumulation, and the percentage of body fat increases with age even if weight does not. However, the relationship between fat and muscle function may not be linear, suggesting that there may be an optimal ratio of lean to fat mass for physical function. There are no definitive pharmacological interventions proven to prevent decline in physical function either by modulating body composition or by other means. One exception may be angiotensin-converting enzyme inhibitors (ACEIs). ACE is an important component of the renin-angiotensin system, the central hormonal regulator of blood pressure. Recent evidence suggests that ACEIs may improve physical function by means of direct effects on body composition in older persons, rather than through its blood-pressure-lowering effects. Clinical and genetic studies in humans and experimental evidence in animals suggest that modulation of the renin-angiotensin system is associated with metabolic and biochemical changes in skeletal muscle and fat, changes that are associated with declining physical function. ACEIs may modulate this process through a variety of molecular mechanisms including their influence on oxidative stress and on metabolic and inflammation pathways. This review describes potential biological mechanisms of ACE inhibition and its contribution to declining physical performance and changing body composition. Promising pharmacoepidemiological studies and experimental evidence in animals suggest that there are appropriate models in which to study this effect. Copyright 2005 by The Gerontological Society of America.