Physical activity is necessary for life and is one of the greatest opportunities to improve the health of populations, although it is sometimes mixed up with sports which can cause injuries or acute cardiac events. Nevertheless, some sedentaries can present with metabolic adverse responses after initiation of a well-planned, health-enhancing physical activity program. This sort of exercise intolerance has some genetic roots and does not necessarily imply that all physical activity should be stopped, but rather must be considered as a side effect of therapy that needs optimizing. Individualization of exercise prescription will always consider follow-up and has to be dynamic according to observations made with the patient.