Global tissue hypoxia is one of the most important factors in the development of multisystem organ dysfunction. In hemodynamically unstable critically ill patients, central venous oxygen saturation (Scvo₂) and mixed venous oxygen saturation (Svo₂) monitoring has been shown to be a better indicator of global tissue hypoxia than vital signs and other clinical parameters alone. Svo₂ is probably more representative of global tissue oxygenation, whereas Scvo₂, is less invasive. Svo₂ and Scvo₂ monitoring can have diagnostic and therapeutic uses in understanding the efficacy of interventions in treating critically ill, hemodynamically unstable patients.