Throughout human history, light has played an important role in medicine. New optical techniques, many involving light emitting diodes, lasers, and fiber optics, are revolutionizing the field of diagnostic monitoring and therapy. Although at an adolescent stage, the power and potential of optical techniques, especially in monitoring blood and tissue oxygenation, has been well recognized, but is still rapidly developing. This review will cover various optical techniques currently used in the in vivo measurement of blood and tissue oxygenation, both in clinical and research settings. These include some well-established techniques such as pulse oximetry, fiber optic venous oximetry, and near-infrared spectroscopy, as well as other techniques that are not yet widely used such as white light spectrophotometry and fluorescence quenching. The review will describe the principles and applications of these techniques, in an attempt to illustrate their capabilities and limitations in measuring oxygenation in blood and tissues.