Résumé : S-100 protein is an acidic calcium-binding protein with a molecular weight of 21 kDa consisting of two submits alpha and beta, which are combined to give alphaalpha (S-100a), alphabeta (S-100a) and betabeta (S-100b) dimeric forms. S-100 protein is much more abundant in the brain than in other tissus and is present as a mixture of S-100a and S-100b (named S-100beta). These two isoforms are predominantly synthesized and secreted by glial cells. Structural damage of these cells causes leakage of S-100beta protein into the extracellular compartment and into cerebrospinal fluid, further entering the bloodstream. We provide here an overview of the physicochemical properties of S-100beta protein, of its pathological aspects and of possible interest in measuring this protein in biological fluids during cerebral diseases and brain damage occurring after surgical events.