Acute respiratory distress syndrome (ARDS) is a heterogeneous disorder that may be triggered by myriad etiologies (both pulmonary and extrapulmonary). Mortality rates for ARDS range from 30 to 75%, and most deaths are a consequence of multiorgan failure (MOF). Since the sentinel description of ARDS in 1967, criteria for the diagnosis of this entity were refined. In 1992, diagnostic criteria for ARDS were published in an American-European Consensus Conference and the term acute lung injury (ALI) was adopted to encompass patients with a spectrum of less severe forms of the same pathological entity. This review discusses limitations of various criteria utilized to diagnosis ARDS and ALI, and why some criteria may be problematic when designing clinical trials. Also discussed are the myriad causes of ARDS, incidence, epidemiology, mortality, and factors that influence outcome.