The focus of this paper will be in the development and in vivo applications of new custom made photoplethysmographic (PPG) and pulse oximetry optical and fiber optic sensors and instrumentation in an effort to investigate their suitability in the estimation of blood oxygen saturation and their contribution in the assessment of organ/tissue perfusion and viability. The paper describes the development of optical and fiber optic PPG and blood oxygen saturation (SpO2) sensors and covers examples of application areas including real-time PPG monitoring from body cavities (esophagus) and solid or hollow organs (bowel, liver, stomach, brain, etc). The clinical studies presented successfully demonstrated the feasibility in acquiring PPGs and estimating blood oxygen saturation values from a variety of organs and tissues. The technological developments and the measurements presented in this work pave the way in a new era of pulse oximetry where direct and continuous monitoring of blood oxygen saturation of internal organs and tissues could be made possible.