Sepsis is a malignant intravascular inflammation representing the body's response to overwhelming and life-threatening infection. Sepsis can result in tissue damage, organ failure, and death. Critical care nurses are at the forefront for identifying sepsis and initiating the early goal-directed therapies that are known to improve survival. Among key factors in the successful resuscitation and stabilization of the septic patient are fluid management, establishment and maintenance of a secure airway, judicious use of pharmacological agents, and dynamic adjustments in therapy based on nuances detected in data from clinical monitoring.