Bioglass 45S5 is used in the medical field as a bone regenerative material. In fact, when immersed in body fluid, a layer of hydroxy carbonate apatite (HCA), an analogue to the mineral phase that bones are made of, is deposited on its surface. A mechanism that would explain this process has been hypothesized and includes cation leaching from the glass to the solution and formation of both a silica-rich layer and a Ca/P-rich surface layer, prior to the actual crystallization of HCA. The present paper analyzes the dissolution of 2-mu m-size particles of Bioglass in TRIS-buffered solution, focusing on the modifications occurring at the surface of the particles. Results from Transmission FT-IR, Raman, and X-ray Photoelectron Spectroscopy were compared in order to obtain this information. In all cases, precise spectral band assignments were obtained by comparing Bioglass spectra, before and after reaction, with the spectra registered on some selected reference samples. The results confirm the hypothesized mechanism of Bioglass reactivity and yield new insights on the surface modifications of the samples. In particular, the following is shown: the strength of the surface H-bonding system and of water coordination decreases during the reaction; surface carbonates, initially mainly bound to Na, are substituted by an increasing amount of Ca-bound carbonates; and the final calcium phosphate layer obtained is very similar, but not identical, to carbonated hydroxyapatite.