Severe sepsis and septic shock are common causes of morbidity and mortality. Interventions directed at specific endpoints, when initiated early in the "golden hours" of patient arrival at the hospital, seem to be promising. Early hemodynamic optimization, administration of appropriate antimicrobial therapy, and effective source control of infection are the cornerstones of successful management. In patients with vasopressor-dependent septic shock, provision of physiologic doses of replacement steroids may result in improved survival. Administration of drotrecogin alfa (activated), (activated protein C) has been shown to improve survival in patients with severe sepsis and septic shock who have a high risk of mortality. In this article we review the multi-modality approach to early diagnosis and intervention in the therapy of patients with severe sepsis and septic shock.