In vivo chemical sensing can be used to monitor metabolic process of the living organism. Intrinsic indicators such as hemoglobin, myoglobin, cytochromes and NADH allow the tissue O 2 supply to be measured. The photometric analysis demonstrates that the spectra of the indicators within the tissue are distinctly changed, since the indicators are unevenly distributed in a highly scattering medium. This restricts the application of evaluation methods that use only a few wavelengths. It has been shown that the larger information content obtained by scanning an appropriate wavelength range can be used to apply successfully the two-flux theory of Kubelka and Munk. Measurements, e.g., on the surface of the beating heart or of the skin, demonstrate strong local variations of the local O 2 supply as well as its rhythmic changes in time. The state of tissue O 2 supply is characterized by a distinct macro- and microheterogeneity. The heterogeneity can be quantitatively described by histograms or topograms; the rhythmicity by the corresponding power spectra. The results of such analyses demonstrate that monitoring of the heterogeneity is essential and that mean values are often misleading. There are several luminescence-based indicators available by which metabolic processes can be monitored. Experiments show that to obtain reliable results, the indicator must be in a defined environment, for example, incorporated in a polymeric matrix (capsules or membranes). Membranes-shaped optodes are very well suited to monitor tissue heterogeneities. A flexible lightweight thin sensor membrane that does not consume the analyte has practically no affect on the O 2 supply. Since the analyte penetrates into the membranes, optodes allow a new type of sensor, the flux sensor, to be constructed, which promises interesting medical applications. Since the photometric measuring device can be separated from the sensor foil, measurements on moving surfaces are possible. Since radiation of wavelength between 700 and 1100 nm (near infrared) penetrates several centimeters into living tissue, near-infrared spectroscopy (NIRS) is used to monitor the hemoglobin oxygenation and the redox state of cytochrome oxidase within the tissue. Quantitative evaluation is based mainly on the application of the photodiffusion theory. This is a very promising method, but it is still in its initial stages. There are optical methods available to measure arterial or venous blood values non-invasively or invasively. If local skin blood flow is increased to its maximum arterial value, pO 2 and pCO 2 values can be derived from the measurements on the skin surface. Photometry of the absorbance changes connected with the arterial pulse is used to monitor arterial HbO 2 saturations (pulse oxymetry). Newly developed phosphorescence indicators bound to albumin are available, which after injection can be used to monitor the PO 2 distribution within the surface vessels of an organ. For invasive measurements catheters or light guides are available to obtain suitable photometric signals. Light guides have been equipped with luminescence-based optical sensors. The big problem for measurement over a long period is still the danger of blood clotting, especially at low blood-flow velocities. The above description of the available and developing optical sensing systems show that optical sensors will become an important diagnostic tool, especially for non-invasive bedside monitoring.