Recent advances in nitric oxide (NO) research have begun to elucidate the roles of NO in sepsis and infection. Although adequate levels of NO production are necessary to preserve perfusion and carry out cytoprotective functions in sepsis, overproduction appears to contribute to hemodynamic instability and tissue damage. These observations have led to the development of strategies to inhibit NO synthesis or scavenge excess NO in patients with septic shock. Local expression of the inducible NO synthase also has antimicrobial functions. The combination of NO with superoxide forms peroxynitrite which participates in bacterial killing in the peritoneal cavity. The capacity of red blood cells and hemoglobin to remove NO most likely accounts for the adjuvant effect of blood in peritonitis. This review will summarize the pathobiology of NO in surgical sepsis and infection.