Exercise has a variable effect on the immune system. The underlying reasons for this variability are multifactorial and include infectious, neuroedocrine, and metabolic factors, with nutritional status of the athlete and the training load playing a role. Environmental factors such as living quarters, travel requirements, and the type of sport (team versus individual) also contribute to infectious risk. Regarding the direct effect of exercise on the immune system, moderate exercise seems to exert a protective effect, whereas repeated bouts of strenuous exercise can result in immune dysfunction. Understanding the relationship between exercise and infectious disease has important potential implications for public health and for clinicians caring for athletes and athletic teams.