Sepsis is a multifaceted and complex medical condition that consumes a vast array of critical care resources and creates an exceptionally difficult clinical challenge for critical care clinicians. As a result, many initiatives over the past decade have been set in motion with the goal of improving the clinical care of patients with sepsis. This article provides a review of the consensus definitions of sepsis and the status of current treatment initiatives for sepsis. The focus of this article is to review the evidence supporting the current clinical practice guidelines with regard to the continuous physiologic monitoring of temperature, blood pressure, heart rate, and respiratory rate. These parameters were chosen because they are recommended by both current consensus practice guidelines and early goal-directed therapy practice. In addition, they are continuously or frequently monitored in the setting of critical care, and though nonspecific for sepsis, as a group they may identify septic patients or those at risk for sepsis. Because critical care nurses are responsible for the continuous monitoring of patients at risk for developing sepsis, they may be able to observe the convergence of nonspecific diagnostic criteria and physical assessment cues early in the development of the condition and positively affect outcomes.