Optimal athletic performance depends on proper function of many organs, including the blood. This is underscored by the focus of endurance athletes on increased hemoglobin through training at altitude or exogenous erythropoietin. Several other aspects of the hematologic system can also affect or be influenced by physical activity. In this article, the authors briefly discuss inherited abnormalities of the blood that can manifest themselves in athletes. We then discuss the effects of exercise on the blood, and acquired abnormalities of blood cells or coagulation parameters that occur in athletes, and that can influence performance or cause other symptoms.