Clinicians who treat patients with acute respiratory distress syndrome (ARDS) use information and guidance from a wide array of sources, ranging from laboratory experiments, clinical data, health services research, intuition, to personal experience. Each of these sources of information brings unique methodology and information, but each is inherently limited. Because ARDS is a syndrome (and not a disease), the clinician or scientist must take additional care when applying knowledge to individual patients among a group, because patients often do not have identical lung pathophysiology. However, an overwhelming body of knowledge has accumulated in the field from multiple sources. In this review, we describe the nature of some of these sources as they relate to ARDS and review examples of when they have succeeded (and sometimes failed) in shaping practice or advancing knowledge about ARDS.