Carriers of a single sickle cell gene mutation generally enjoy normal lifespans without serious health consequences related to their sickle cell status, but under extreme conditions such as severe dehydration and high-intensity physical activity, complications such as exertional rhabdomyolysis, splenic infarction, and papillary necrosis can occur. Recently, the National Collegiate Athletic Association (NCAA) adopted a policy that requires sickle cell solubility testing for all incoming student athletes. However, the American Society of Hematology (ASH) and other physician organizations oppose this policy. What is the basis for this controversy and how have new findings moved the field forward? I discuss herein the epidemiology, genetics, and clinical studies of sickle cell trait; review the implications of current policies regarding sickle cell trait screening and interventions for the student athlete; and examine additional areas where more information is needed.