Bone tissue engineering has attracted considerable attention as a promising treatment modality for severe bone degeneration. The pressing need for more sophisticated and fully functional bone substitutes has spurred a refocus on the development of bone constructs in a way more comparable to the physiological process. Current research is increasingly revealing the central roles of macrophages/monocytes in regulating bone development and repair, so we propose that these immunocytes can play a similar pivotal role in directing engineered bone regeneration. Accordingly, we discuss two possible strategies to exemplify how the distinctive power of macrophages/monocytes – particularly their cytokine-secretion ability and chemotactic response to foreign materials – can be harnessed to enhance the performance of bone tissue engineering applications