The pathophysiology of sepsis can be regarded as a series of steps, beginning with the invasion of normally sterile tissue by microbes and the elaboration of various pro-inflammatory mediators. The final common pathway is often the development of the multiple organ dysfunction syndrome (MODS). Whereas a great deal has been learned during the past quarter century about the inflammatory processes associated with sepsis (and other related conditions, such as ischemia/reperfusion injury), our understanding is far less developed with respect to the pathophysiological events that lead to organ dysfunction under these conditions. Nevertheless, efforts by both clinical and laboratory scientists are leading to new knowledge in this area. The chapters in this volume provide a state-of-the-art overview of many aspects of the pathophysiology of organ dysfunction in critical illness.