With improvement in supportive care patients rarely die from their presenting illness but rather from its sequela, namely sequential multi-organ failure. Tissue hypoxia is believed to be the causation of multi-organ dysfunction syndrome (MODS). The expedient detection and correction of tissue hypoxia may therefore limit the development of MODS. The standard oxygenation and hemodynamic variables (blood pressure, arterial oxygenation, cardiac output) which are monitored in critically ill patients are 'upstream' markers and provide little information as to the adequacy of tissue oxygenation. Global 'downstream' markers such as mixed venous oxygen saturation and blood lactate are insensitive indicators of tissue hypoxia. Sublingual PCO(2) is a regional marker of microvascular perfusion and tissue hypoxia that holds great promise for the risk stratification and end-point of goal directed resuscitation in critically ill patients. This paper reviews the technology and application of sublingual PCO(2) monitoring.