Frailty is a state of reduced physiologic reserve associated with increased susceptibility to disability. Reduced physiologic capacity in neurologic control, mechanical performance, and energy metabolism are the major components of frailty. Although disease is an important cause of frailty, there is sufficient epidemiologic and experimental evidence to conclude that frailty is also due to the additive effects of low-grade physiologic loss resulting from a sedentary lifestyle and more rapid loss due to acute insults (illness, injuries, major life events) that result in periods of limited activity and bedrest. The pathogenesis of frailty involves a complicated interaction of factors that block recovery from rapid physiologic loss. To some extent, frailty is preventable. Approaches to prevention include (1) the periodic monitoring of key physiologic indicators of frailty, (2) the prevention of physiologic loss and acute and subacute episodes of physiologic loss, (3) the prediction of episodes of physiologic loss and the reduction of frailty prior to the loss, and (4) the removal of obstacles to recovery once physiologic loss has occurred.