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Pulse oximetry is a noninvasive photometric technique that provides information about arterial blood oxygen saturation (SpO2) and heart rate and has widespread clinical applications. This is accomplished via peripheral pulse oximetry probes mainly attached to the finger, toe, or earlobe. The direct application of pulse oximetry to an organ, such as the esophagus, liver, bowel, stomach or free flap, might provide an indication of how well perfused an organ or a free flap is. Also, the placement of a pulse oximetry probe at a more central site, such as the esophagus, might be more reliable at a time when conventional peripheral pulse oximetry fails.The focus of this article is the development and in vivo applications of new custom-made photoplethysmographic (PPG) and pulse oximetry optical and fiberoptic probes and instrumentation in an effort to investigate their suitability for the estimation of arterial blood oxygen saturation at different organs and tissues. The article will cover examples of application areas including real-time PPG and SpO2 monitoring for the esophagus and solid organs, including free flaps, using custom-made probes.Clinical studies have successfully demonstrated the feasibility of acquiring PPGs and estimating arterial blood oxygen saturation values from a variety of organs and tissues.The technological developments and the measurements presented in this work pave the way to a new era of pulse oximetry where direct and continuous monitoring of blood oxygen saturation of internal organs and tissues (esophagus, bowel, liver, stomach, free flaps) could be possible.