Mobility is the most studied and most relevant physical ability affecting quality of life with strong prognostic value for disability and survival. Natural selection has built the “engine” of mobility with great robustness, redundancy, and functional reserve. Efficient patterns of mobility can be acquired during development even by children affected by severe impairments. Analogously, age-associated impairments in mobility-related physiological systems are compensated and overt limitations of mobility only occur when the severity can no longer be compensated. Mobility loss in older persons usually results from multiple impairments in the central nervous system, muscles, joints, and energetic and sensory physiological systems. Early preclinical changes in these physiological systems that precede mobility loss have been poorly studied. Peak performance, rate of decline, compensatory behaviors, or subclinical deterioration of physiological resources may cumulatively influence both timing of mobility loss and chances of recovery, but their role as risk factors has not been adequately characterized. Understanding the natural history of these early changes and intervening on them would likely be the most effective strategy to reduce the burden of disability in the population. For example, young women with low bone peak mass could be counseled to start strength resistance exercise to reduce their high risk of developing osteoporosis and fracture later in life. Expanding this approach to other physiological domains requires collecting and interpreting data from life course epidemiological studies, establishing normative measures of mobility, physical function, and physical activity, and connecting them with life course trajectories of the mobility-relevant physiological domains.