Although the central nervous system is the primary endpoint of most general anesthetics, it is still the least monitored organ in clinical anesthesiology. In the last decade, technological research has expanded the application of near-infrared spectroscopy to allow continuous, non-invasive, and bedside monitoring of cerebral oxygen saturation (rSO(2)) through the scalp and skull, providing accurate information on the balance between brain oxygen supply and demand. The aim of this review is to provide an overview on relevant technological issues of cerebral oximetry, describe a systematic approach to its use, and summarize current information on its possible impact on our daily practice. We reviewed studies published on peer-reviewed journals about technological development and clinical application of rSO(2) monitoring in different fields of application to clinical practice. Due to the wide patient-to-patient variability of baseline rSO(2) values in each patient the baseline value should be determined before inducing general anesthesia, and cerebral ischemia is related more to the changes from baseline than to the absolute value: a reduction of 20% from baseline is usually accepted as clinical threshold of cerebral ischemia. If baseline rSO(2) is lower than 50% the critical threshold should be reduced to 15%. Routine use of rSO(2) monitoring in patients undergoing cardiac surgery to guide the anesthesia plan has been demonstrated to improve patient outcome and shorten hospital stay. However, rSO(2) monitoring does not seem to provide information accurate enough to indicate the placement of a Javid's shunt during carotid endarterectomy. In patients with neurological pathology or head trauma rSO(2) monitoring has been reported accurate enough in detecting early changes in cerebral blood flow that might result in cerebral ischemia. In aged patients undergoing major abdominal surgery rSO(2) monitoring to guide the anesthesia plan has been reported to reduce the exposition to cerebral ischemia with less effects on cognitive decline and shorter hospital stay. In conclusion several clinical conditions routinely encountered in our daily practice have the potential to disrupt the balance between the brain oxygen supply and demand, exposing to the risk of intraoperative cerebral ischemia. These alterations in brain oxygen balance remain totally undiagnosed if we do not specifically monitor it; while the possibility of monitoring regional cerebral oxygen saturation through a simple and totally non-invasive device has the potential for optimizing our anesthesia plan to the real needs of our main targeted organ: the brain.