The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality around the world. In the United States alone there are 150,000 cases per year. Although there have been significant scientific advances in understanding the clinical and pathophysical aspects of the syndrome, there is as yet no specific therapy for ARDS. Moreover, although major risk factors for the development of ARDS include sepsis, aspiration, and multiple trauma, only a minority of patients with these risk factors develop ARDS. Individual differences in susceptibility to chronic disease have been a subject of active molecular epidemiologic investigations for the past decade. In particular, risk factors for cancer conferred by heritable polymorphisms and various metabolic functions have been reported. More recently, a polymorphism of endothelial nitrate oxide synthase has been associated with an increased susceptibility to coronary-artery disease, and polymorphisms in GSTM1 have been associated with an increased risk of developing asbestosis. A recent study of tumor necrosis factor (TNF) polymorphisms has been associated with poor outcome in ARDS.