Many epidemiological studies have indicated a protective role for a diet rich in fruits and vegetables against the development and progression of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. Physical inactivity and unhealthy eating contribute to these conditions. This article assesses the scientific rationale of benefits of physical activity and good nutrition on CVD, especially on atherosclerosis-related diseases. Compelling evidence has accumulated on the role of oxidative stress in endothelial dysfunction and in the pathogenesis of CVD. Reduced nitric oxide (NO) bioavailability due to oxidative stress seems to be the common molecular disorder comprising stable atherosclerotic narrowing lesions. Energy expenditure of about 1000 kcal (4200 kJ) per week (equivalent to walking 1 h 5 days a week) is associated with significant health benefits. Such benefits can be achieved through structured or nonstructured physical activity, accumulated throughout the day (even through short 10-min bouts) on most days of the week. Some prospective studies showed a direct inverse association between fruit and vegetable intake and the development of CVD incidents such as acute plaque rupture causing unstable angina or myocardial infarction and stroke. Many nutrients and phytochemicals in fruits and vegetables, including fiber, potassium, and folate, could be independently or jointly responsible for the apparent reduction in CVD risk. Novel findings and critical appraisal regarding antioxidants, dietary fibers, omega-3 polyunsaturated fatty acids (n-3 PUFAs), nutraceuticals, vitamins, and minerals, are presented here in support of the current dietary habits together with physical exercise recommendations for prevention and treatment of CVD.