Cardiovascular disease (CVD) is the leading cause of death in the United States, resulting in increased awareness of the preventive importance of regular physical activity. Because athletes are considered physically fit, occurrence of sudden athlete death from CVD is perplexing. Regular intense physical activity can cause changes to the cardiovascular system that mimic known CVD processes. Therefore, screening of athletes for conditions that may increase risk for sudden cardiac death (SCD) is challenging. This article focuses on this problem, discussing the athlete's heart, SCD and associated CV conditions, and preparticipation screening. We also review recommendations of the 26th Bethesda Conference on determining eligibility for competition in athletes with known CV abnormalities, and how the recommendations relate to individual disease processes.