The definition of biomaterial as proposed by the European Society for Biomaterials in 1986 puts forward the overall importance of the notion of contact between the biomaterial and biological medium (cell, tissue, fluid,...). The underlying concept of biocompatibility makes the interface between biomaterial and biological medium a privileged zone of interest. In this paper, we would like to give an exhaustive view of how ion beams techniques can contribute to a better understanding of such interface taking several examples dealing with bone tissue substitution. After a short presentation of ion beams techniques the paper will focus on PIXE/RBS spectroscopies and will give the basics of these coupled technique. Three examples will then be presented to illustrate the interest of these techniques to study biomaterials/biological interactions. The first example deals with metallic alloys based joint prostheses. The ionic release from the prosthesis and the wear behavior of total knee prostheses will be presented. In the last two examples, bioactive materials will be studied. The common characteristic of bioactive ceramics is the kinetic modification of their surface upon interaction which is ideally monitored by PIXE chemical mapping. The second example will review the benefit of using PIXE/RBS technique to study the effect of doping of bioactive glasses on the very first steps involved in the bioactivity mechanisms like dissolution, ionic release, and biomineralization onto the surface of the glasses. Finally, protein delivery systems based upon mesoporous hydroxyapatites will be studied. Chemical mapping allowing the quantitative determination of protein distribution inside the HAp grains will be presented for the first time.