Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy. Understanding the pathophysiology of sepsis enables clinicians to institute rational intervention directed towards the pathophysiological mechanisms. This article reviews definitions of sepsis and offers a brief overview of ist pathophysiology. Current knowledge on the pathophysiological mechanism of cytokines and modulation of systemic cytokine levels during sepsis and septic shock is discussed. The important role of cytokines in sepsis and septic shock may require more detailed investigations of the cytokine pathophysiological network.