Since its first description 50 years ago, no other intensive care syndrome has been as extensively studied as acute respiratory distress syndrome (ARDS). Despite this extensive body of research, many basic epidemiologic questions remain unsolved. The lack of gold standard tests jeopardizes accurate diagnosis and translational research. Wide variation in the population incidence has been reported, making even simple estimates of the burden of disease problematic. Despite these limitations, there has been an increase in the understanding of pathophysiology and important risk factors both for the development of ARDS and for important patient-centered outcomes like mortality. In this Critical Care Perspective, we discuss the historical context of ARDS description and attempts at its definition. We highlight the epidemiologic challenges of studying ARDS, as well as other intensive care syndromes, and propose solutions to address them. We update the current knowledge of ARDS trends in incidence and mortality, risk factors, and recently described endotypes.