It is widely known that a regular physical activity of mild intensity results in significant benefits in term of health, while a sedentary lifestyle contributes, together with other risk factors, to development of chronic degenerative diseases, in particular cardiovascular, metabolic and osteoarticular diseases. Many evidences show an inverse relation between mortality/morbidity and physical activity. Furthermore the advanced age does not contraindicate physical activity and exercise can prevent cardiovascular and osteoarticular diseases in the elderly. Physical exercise in the elderly is able to: a) improve muscular tone and movement skills, b) reduce osteoporosis effects, c) induce an increased release of neuro- ormonal mediators as endorphins and serotonin, d) reduce the risk of sudden death caused by cardiovascular diseases, e) reduce the development of tumors and metabolic disorders, f) delay the decline of cognitive function. The objective of this literature review is to clarify the link between physical activity, aging and aged- related diseases, underlining pathophysiological and molecular mechanisms, and, whenever possible, to provide practical guidelines for physical activity that is useful and acceptable even by older people emphasizing that an adequate exercise must a) be adapted to the capacity of the subject, b) be prescribed after careful evaluation of environmental conditions under which it must be practiced, c) be congenial and suitable compared to the cultural, ideational and emotional abilities of the subject and, finally, d) be integrated in a comprehensive program of active lifestyle. In conclusion, a program of physical activity is a beneficial and safe indication both in elderly without overt diseases and in the frail elderly.