The propensity for regular and repeated physical exercise to induce and maintain ahormesic effect upon health parameters over a broad range of disorder conditions through the progression of resilience to neurodegenerative disorders, diabetes, stroke, sarcopenia, osteopenia, immunosenescence, and metabolic syndrome has been examined. Beyond the alleviation fragility, fatigue, stress-distress and selective vulnerability perturbations induced by different forms of physical exercise may induce hormesis and/or autophagy, through the disruption of homeostasis and manifestation of adaptive responses, to instigate multi-layered resilience. The hormesis challenges, accomplished through daily exercise, the promotion of resilience at molecular, cellular, tissue, e.g. muscle, and organ, e.g. brain, immune-functioning, bone material, physiological and behaviour-expressive levels, have been observed both from pathophysiological and etiogenetic dimensions. Regular exercise over extended periods (optimally years and decades, preferably lifelong) is expected to shift the inverted-U shaped hormesis curve to the right thereby conferred resistance to disease and ill-being and ensuring strength and health advantages. It seems likely that chronic, regular exercise, consisting of suitable proportions of endurance and resistance type, performed daily over months, years or decades ought to instigate some manner of ‘behavioural sensitization’ whereby the health benefits of equivalent levels of exercise escalate incrementally.