Septic shock is mediated by complex interactions of cells, cytokines, and humoral pathways. Clinical therapeutic strategies aimed at inhibiting selected pathways have been efficacious in subsets of patients. Experimental studies focusing on the activities of single cytokines have contributed to the understanding of the complex pathophysiology of septic shock. More precise delineation of the roles of each mechanism contributing to pathogenesis will permit the identification of subsets of patients who might benefit from particular therapeutic strategies and will guide the development of additional approaches to prevention and treatment.