The use of pulmonary artery catheters has diminished, so that other technologies are emerging. Central venous oxygen saturation measurement (ScvO₂) as a surrogate for mixed venous oxygen saturation measurement (SvO₂) is simple and clinically accessible. To maximize the clinical utility of ScvO₂ (or SvO₂) measurement, it is useful to review what the measurement means in a physiologic context,how the measurement is made, important limitations, and how this measurement may be helpful in common clinical scenarios. Compared with cardiac output measurement, SvO₂ is more directly related to tissue oxygenation. Furthermore,when tissue oxygenation is a clinical concern, SvO₂ is less prone to error compared with cardiac output, where small measurement errors may lead to larger errors in interpreting adequacy of oxygen delivery. ScvO₂ should be measured from the tip of a central venous catheter placed close to, or within, the right atrium to reduce measurement error. Correct clinical interpretation of SvO₂, or its properly measured ScvO₂ surrogate, can be used to (1) estimate cardiac output using the Fick equation, (2) better understand whether a patient's oxygen delivery is adequate to meet their oxygen demands, (3) help guide clinical practice, particularly when resuscitating patients using validated early goal directed therapy treatment protocols, (4) understand and treat arterial hypoxemia, and (5) rapidly estimate shunt fraction (venous admixture).