Severe sepsis is sepsis associated with acute organ dysfunction. Septic shock in turn, implies severe sepsis that has led to circulatory shock refractory to fluid resuscitation alone. The immediate approach to severe sepsis follows the ABCs of resuscitation: Airway, Breathing, and Circulation. Special emphasis on the circulation involves early goal-directed therapy, adequate fluid resuscitation, and vasopressor/inotropic support. Once the patient's cardiorespiratory status is stabilized, efforts must be directed at uncovering the source and empirically yet accurately treating the infective underpinnings of severe sepsis. Following that, each of the patient's other organ systems at risk needs to be addressed: Renal/metabolic, gastrointestinal, hematological, and endocrine. Novel treatments will target both the proinflammatory and procoagulation cascades of sepsis.