Septic shock is a multisystem disorder that represents the host's response to microbial invasion in its most fulminant form. One of the critical defects is a widespread inability to use available substrate for energy production. Endogenous mediators, particularly the cytokines, appear to play an essential role in this defect and in the entire host-mediated cascade. Traditional therapy remains primarily supportive. However, newer, investigational forms of therapy show promise by more directly treating the underlying disturbances.