Acute lung injury (ALI) remains a serious threat to critically ill patients and continues to pose challenges to clinicians and investigators as they strive to better identify and treat these patients. Over 30 years of clinical and basic science investigations have led to a better understanding of the pathophysiology, risk factors, and prognosis of this entity but we still lack a "gold standard'' for its identification. The American-European Consensus Conference definition has helped in the effort to standardize the definition of ALI but is still fraught with difficulties in the application of criteria for the chest radiograph, hypoxemia, and left atrial hypertension. As further efforts are undertaken to better define ALI and to more accurately describe its incidence, it is critical that methodology to assess the accuracy and reliability of such definitions be utilized. This union of clinical epidemiology, clinical research, and basic science will not only better describe the population burden of ALI but will also better track the effect of current and future therapeutic interventions.