Appropriate physical activity is one of the bases of healthy lifestyle. In fact, physical exercise and playing sport may be associated with both improvements and injury to both general and reproductive health. A biologically normal testosterone secretion appears fundamental in males to guarantee both a physiological exercise adaptation and safe sport participation. The reproductive system is highly sensitive to the effects of exercise-related stress and the reproductive hormones may both increase and decrease after different acute or chronic exercises. Exercise and sport participation may positively or negatively influence andrological health status depending on the type, intensity and duration of performed physical activity and on individual health status. In addition, prohibited substances administration (e.g. androgenic-anabolic steroids, and so forth) in competitive and non-competitive athletes represents the main cause of iatrogenic andrological diseases. Preventing and treating andrological problems in active healthy and unhealthy individuals is as important as promoting a correct lifestyle. Physicians need to be educated on the relationships between the male reproductive system and sport participation and on the great role of the pre-participation physical examination in the prevention of andrological diseases.