The underlying concepts of biocompatibility, biomimetism, and bioactivity make the interface between biomaterials and biological medium a privileged zone of interest. This talk will 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. Knowledge of the elemental distribution of the local concentration and chemical nature of ions at the biomaterials/living tissues interface is primordial to understand the complex interfacial reactions and physico-chemical properties of materials involved during the material integration, biomimetism processes, and bone bonding. Moreover, quantitative chemical mapping of relevant bone trace elements can permit improvement in the quality and above all the functionality of these biomaterials. These elements released in trace quantities physiologically interesting can induce specific cellular responses. Thus, it is important to study at the micrometer and nanometer scale interfaces that biomaterials develop in vitro and in vivo. Ion beam methods of analysis like PIXE, RBS, and STIM are very useful to determine simultaneously multielemental maps and concentration measurements of major, minor, and trace elements with a good spatial resolution. Thanks to the last instrumental developments of accelerators, ion beams from micrometer to nanometer are obtained.