Nitric oxide is one of the most versatile molecules produced by mammalian cells. Its role in sepsis and inflammation has been the subject of intense investigation since its discovery as a cell product in 1987. The role of arginine in sepsis and trauma has also received considerable attention, but most of the earlier studies on arginine preceded the studies on nitric oxide and the discovery that arginine serves as the nitrogen donor for nitric oxide synthesis. This review will explore the role that nitric oxide plays in sepsis and the effects of arginine metabolism on nitric oxide synthesis.