There are myriad ways in which optimal levels of physical activity over the course of the life span could potentially contribute to the prevention of functional disability in old age. These include direct effects of exercise to maximize physiologic capacity and prevent or delay the onset of disability-related conditions and more indirect effects, such as the modulation of psychosocial factors important in the expression of disability. Epidemiologic studies strongly suggest that functional disability is inversely related to physical activity level or physical fitness in various domains. Experimental studies confirm the benefits of exercise on correlates of disability, such as impairments of muscle strength or performance-based tests of functional limitations. However, the evidence that exercise can actually prevent disability in the long-term is not yet established by data from randomized clinical trials in the general population. Secondary prevention of disability in frail elders has been shown in a few trials. The available evidence, however, suggests that a rational exercise prescription for the prevention and treatment of disability at this time should include promotion of a physically active lifestyle and specific exercises targeting aerobic capacity, strength, and balance. Differential emphasis on specific elements of this prescription may be necessary and appropriate, depending on the etiology of the disability in specific cohorts, severity of physical impairments and functional limitations, and other individual characteristics relevant to exercise feasibility, safety, and efficacy.