Conventional cardiovascular monitoring may not detect tissue hypoxia, and conventional cardiovascular support aiming at global hemodynamics may not restore tissue oxygenation. NIRS offers non-invasive online monitoring of tissue oxygenation in a wide range of clinical scenarios. NIRS monitoring is commonly used to measure cerebral oxygenation (rSO(2)), e.g. during cardiac surgery. In this review, we will show that tissue hypoxia occurs frequently in the perioperative setting, particularly in cardiac surgery. Therefore, measuring and obtaining adequate tissue oxygenation may prevent (postoperative) complications and may thus be cost-effective. NIRS monitoring may also be used to detect tissue hypoxia in (prehospital) emergency settings, where it has prognostic significance and enables monitoring of therapeutic interventions, particularly in patients with trauma. However, optimal therapeutic agents and strategies for augmenting tissue oxygenation have yet to be determined.