Homo sapiens are evolutionarily adapted to be very physically active throughout life, and thus habitual physical activity (PA) is essential for well-being and longevity. Never the less, middle-aged and older individuals engaging in excessive strenuous endurance exercise appear to be at increased risk for a variety of adverse cardiovascular (CV) effects including atrial fibrillation, myocardial fibrosis, and coronary atherosclerosis. An emerging body of evidence indicates U-shaped or reverse J-shaped curves whereby low doses and moderate doses of PA significantly reduce long-term risks for both total mortality and CV mortality, however, at very high doses of chronic strenuous exercise much of the protection against early mortality and CV disease is lost. The optimal dose, or what we term 'Goldilocks Zone,' of PA may be: at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous-intensity aerobic activity, but not more than four to five cumulative hours per week of vigorous (heart-pounding, sweatproducing) exercise, especially for those over 45 years of age. It is also important to take at least one day per week off from vigorous exercise. There appears to be no concerns about an upper threshold for safety for leisure-time low-to-moderate intensity activities such as walking at a comfortable pace, housework, gardening, etc. After every 30 consecutive minutes spent sitting, stand up and move, ideally walking briskly for about five minutes.