In the initial treatment of a critically ill patient, blood pressure, heart rate, urine output, and central venous pressure guide resuscitative efforts. Despite normalization of these variables, global tissue hypoxia may still persist and has been implicated in the development of multiorgan failure and increased mortality. Definitive management includes intensive care unit admission, pulmonary artery catheterization using mixed venous oxygen saturation (SvO2), and hemodynamic optimization. In the absence of or before definitive management, hemodynamic optimization can be performed using central venous oxygen saturation (ScvO2) as a surrogate. The physiology, technology, clinical uses, and rationale for ScvO2 monitoring are reviewed, including issues regarding physiologic equivalence to SvO2. The clinical use of ScvO2 monitoring, evidence-based outcome implications, and limitations of ScvO2 monitoring will also be examined.