Nowadays, with global population aging and habits, cases of fracture, wear and bone loss have constantly concerned health authorities. As an alternative for the recovery of such patients and the promotion of better living conditions, there is a pressing need for development of biomaterials that can successfully replace or regenerate bone tissue. In this research area, microespheres deserve great attention due their unique properties. The specific material and the characteristics of the microspheres to be used for bone regeneration depend on each specific situation, taking into account aspects such as bone characteristics, injury size and selection of the most appropriate technique for such treatment. Generally, microspheres can act as a scaffold for the temporary or permanent filling of the injured area, or may act as a controlled drug delivery system. Moreover, the microspheres can simultaneously fulfill both functions. In this chapter, an overall view of bone tissue is presented, including the structure and functions. The main aspects of bone regeneration are briefly discussed, considering its fracture self-repairing mechanisms through reabsorption and deposition of the mineralized matrix process. When such mechanisms are not enough to provide full recovery, tissue regeneration strategies for such repairs are presented, highlighting the use of biomaterials and specifically microspheres. Finally, some examples of microsphere application to different situations related to the bone regeneration process are discussed.