Sepsis, septic shock and organ failure are common among patients with moderate to severe burns. The inability of demographic and clinical factors to identify patients at high risk for such complications suggests that genetic variation may influence clinical outcome. Moreover, the genetic predisposition to death from infection has been estimated to be greater than for cardiovascular disease or cancer . While it is widely accepted that genetic factors influence many complex disease processes, controversy has emerged regarding the most appropriate methods for detection and even the validity of many published allelic associations . This article will review the few studies of genetic predisposition that have been conducted in the setting of burn injury, then discuss some of the obstacles and potential approaches for the discovery of additional allelic associations.