Exercise, as a potent epigenetic regulator, implies the potential to counteract pathophysiological processes and alterations in most cardiovascular/respiratory cells and tissues not withstanding a paucity of understanding the underlying molecular mechanisms and doseresponse relationships. In the present account, the assets accruing from physical exercise and its influence upon executive functioning are examined. Under conditions of neuropsychiatric and neurologic ill-health, age-related deterioration of functional and biomarker indicators during healthy and disordered trajectories, neuroimmune and affective unbalance, and epigenetic pressures, exercise offers a large harvest of augmentations in health and well-being. Both animal models and human studies support the premise of manifest gains from regular exercise within several domains, besides cognitive function and mood, notably as the agency of a noninvasive, readily available therapeutic intervention.