As direct effector cells for osteogenesis, osteoblastic lineage cells are commonly used for evaluating the in vitro osteogenic capacity of bone biomaterials. This strategy achieves certain success in developing novel bone biomaterials. However, inconsistent results between in vitro and in vivo studies are not uncommon. Many potential bone biomaterials developed from the traditional strategy are found to behave undesirably in vivo in term of bone regeneration, indicating the mechanisms that govern the material’s capacity to mediate osteogenesis is still not well understood. Osteoimmunology has revealed the important role of immune cells in the regulation of bone formation and remodelling. This has informed a paradigm shift in developing bone biomaterials from an inert to an osteoimmunomodulatory material, highlighting the importance of immune cells in the material-mediated osteogenesis. Neglecting the importance of the immune response is a major shortcoming in materials assessment, which may be the cause of the inconsistence between in vitro and in vivo conditions. Here we reviewed the interactions between bone cells and immune cells, with an emphasis on how immune cells affect osteogenesis and osteoclastogenesis. The current knowledge of immunoregulation by bone biomaterials is summarized. We propose the important property of osteoimmunomodulation in developing advanced bone biomaterials and bio-mimic in vitro assessment methods for bone biomaterials. It is the ambition of the authors that this review will inform the refinement of a systematic evaluation and development of a new generation of advanced bone biomaterials, in which the importance of osteoimmunomodulatory properties is given full consideration.