Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland and Department of Anesthesiology, University of Maryland, Baltimore, Maryland ndotoxin is a complex lipopolysaccharide molecule situated within the outer membrane of E Gram-negative bacteria. For more than a half century, researchers have used purified endotoxin to investigate the pathophysiologic events associated with septic shock (1, 2). Recently, scientists have studied the effects of antibodies directed against endotoxin in patients with presumed Gram-negative sepsis (3, 4), but the studies, which are considered controversial, have not shown a significant therapeutic benefit and, in addition, have raised new questions about the role of endotoxin in bacterial infections (5). In the United States, sepsis and septic shock lead to over 200,000 deaths each year (6). Septic patients are frequently encountered by anesthesiologists in the operating room and intensive care unit. Using antibiotics, surgical drainage of sequestered infections, and intensive care support, clinicians can help many patients with septic shock, but mortality rates remain high and additional therapies are needed to treat this lethal disease. An understanding of the pathophysiology of sepsis is important for anesthesiologists who treat critically ill patients, and will become increasingly important as new therapies are developed. In this review, we intend to help the clinician better understand the role of endotoxin in septic shock by explaining its structural and functional relationships in human disease. We will also examine new research that uses antiendotoxin therapy as a treatment for sepsis.