Regular physical exercise reduces the risk of lifestyle-related diseases such as diabetes and atherosclerosis and is associated with improved well-being and longer live expectancy.Exercise, therefore, may be prescribed as medicine for primary prevention or adjunctive treatment for a variety of disorders, including obesity, type 2 diabetes, cardiovascular diseases, dementia, and cancer. The beneficial effects of exercise had already been recognized by Hippocrates (c 460–377 BC), a physician living on the Greek island of Kos (Figure 1) and considered the ‘father of medicine’. Hippocrates introduced the concept of ‘physis’ and thereby changed the hieratic or theocratic medicine into a rational discipline. The structure of the Asclepieion of Kos, a healing temple named after Asklepios of Kos, indicates that Hippocrates practiced in a holistic health care model, and in his school science met with drug therapy, diets, and physical exercise. Indeed, patients at the Asclepieion were offered general treatment that included physical exercise and walks considered necessary to restore health. Hippokrates’ advice ‘walking is the best medicine’ can be considered as the first notion of ‘exercise is medicine’, and represents a timeless non-pharmacological prescription for health and longevity.