Septic shock is a major cause of hospital deaths despite modern intensive therapy. Profound hypotension is caused by a collapse of regulatory mechanisms. Recent advances have established that bacterial products and the host inflammatory response together generate uncontrolled production of nitric oxide throughout the vasculature, accounting for this vasodilatation. Progressive heart failure is a further manifestation of established septic shock. Emerging research suggests that overproduction of nitric oxide within the myocardium likewise leads to loss of normal myocardial function. The possibility exists that exciting future therapies will be able to selectively inhibit the overproduction of nitric oxide and aid recovery from this frequently lethal condition.