Severe sepsis is an infection-induced process that often promotes organ dysfunction and death in up to 50% of afflicted patients. Clinical advances that improve patient survival include early goal-directed volume resuscitation, broad-spectrum empiric antimicrobial therapy with deescalation strategies, therapy with drotrecogin alfa (activated), glucocorticoid replacement in patients with adrenal insufficiency, and tight control of blood glucose levels. The challenge for critical care practitioners is to integrate the many pharmacologic and supportive interventions required for optimal care of these patients.