Severe sepsis leading to organ failure is the most common cause of mortality among critically ill patients. Variability analysis is an emerging science that characterizes patterns of variation of physiologic parameters (e.g., vital signs) and is believed to offer a means for evaluating the underlying complex system producing those dynamics. Recent studies have demonstrated that variability of a variety of physiological parameters offers a novel means for helping diagnose, manage, and treat sepsis. The purpose of this literature review is to examine existing data regarding the use of variability analysis in patients suffering from sepsis and to highlight potential uses for variability in improving care for patients with sepsis. Recent articles published on heart rate, respiratory rate, temperature, and glucose variability are reviewed. The association between reduced heart rate and temperature variability and sepsis and its severity, the relationship between augmented glucose variability and mortality risk, and current uses of respiratory rate variability in critically ill patients will all be discussed. These findings represent early days in the understanding of variability alteration and its physiological significance; further research is required to understand and implement variability analyses into meaningful clinical decision support algorithms. Large, multicenter observational studies are needed to derive and validate the associations between variability and clinical events and outcomes in order to realize the potential of variability to change sepsis care and improve clinical outcomes.