Technical progresses make it now possible to monitor well known or new parameters in vivo or in the laboratory with high accuracy. Especially optical sensors can advantageously be used for many medical applications. To understand advantage and limitation of a measuring technique the basic processes will be shortly discussed. There are two types of optical sensors: 1) optical sensors which use intrinsic indicators (as for example haemoglobin or cytochromes). In this chapter tissue photometry and evaluation methods for multicomponent scattering systems are discussed; nearinfrared and NADH fluorescence measurements are shortly mentioned. 2) Optical sensors using extrinsic indicators (optodes). As extrinsic indicators absorbant as well as luminescent indicators are used. Luminescence indicators are especially sensitive. Microoptodes and two dimensional imaging is possible. From the basic molecular reactions of the sensing mechanisms follows that for most of the indicator reactions there is a non-linear, almost hyperbolic relationship between optical signal and concentration of the analyte. Consequently, accuracy as well as sensitivity of the optode is changing in a given measuring range. Therefore, the optical indicator must be carefully selected. Lifetime (or phase angle) measurements have the advantage that their accuracy is independent of indicator concentration, intensity of the light source and light transport between the sensing element and the photometric setup. Optodes can be manufactured as flexible membranes permeable for the analyte. This facilitates the construction of fibreoptic sensors. As practical examples oxygen optodes, ion optodes, optical pCO2 sensors, and bench-top as well as intra-arterial blood gas measurements are discussed in detail.