Infrared spectroscopy is nowadays frequently employed for applications in clinical chemistry. Since blood serves as the primary metabolic transport system in the body, its composition is the preferred indicator with respect to the pathophysiological condition of the patient. An important class of substances are the metabolites, including glucose, which are accessible by direct spectroscopic measurement without sample treatment. Multicomponent assays based on such technology are reagentless, fast and readily automated. Different in-vitro assays using mid- or near-infrared spectral data are presented including results from ex-vivo measurements using microdialysis and ATR spectroscopy for continuous blood glucose monitoring. Non-invasive sensing systems are under development for the determination of blood glucose, especially for diabetic patients or for monitoring in intensive care and surgery. Near-infrared spectrometry of skin tissue has been proposed, which allows a certain tissue volume to be integrally probed. On the other hand, fast measurements, such as used in pulse oximetry, can enable intravascular probing, i.e. collecting information on the arterial part of the vascular system (near-infrared plethysmography). Results and prospects for applications in non-invasive blood component assays are discussed.