In critically ill patients, tissue hypoperfusion is an important cause leading to multi-organ dysfunction and death, and it cannot always be detected by measuring standard global hemodynamic and oxygen-derived parameters. Gastric intramucosal partial pressure of carbon dioxide (PCO2) as measured by gastric tonometry has been recognized to be of clinical value as a prognostic factor, in assessing the effects of particular therapeutic interventions, and as an end-point of resuscitation. However, this technique has several limitations that have hampered its implementation in clinical practice. The sublingual tissue bed has been shown to be damaged in models of shock, and microcirculatory changes in this area may indicate imminent changes in other important organs. The measurement of sublingual mucosal PCO2 (PslCO2) by sublingual capnography is technically simple, noninvasive and gives near instantaneous results. Clinical studies have established that high PslCO2 values and, more especially, high PslCO2 gap (PslCO2 - arterial PCO2) values are correlated with impaired microcirculatory blood flow and a poor outcome in critically ill patients. Sublingual capnography seems to be the ideal noninvasive monitoring tool to evaluate the severity of shock states and the adequacy of tissue perfusion. However, clinical studies are needed to determine the clinical utility of PslCO2 gap monitoring as end-point target to guide resuscitation in critically ill patients.