Fluid flow-induced forces play a key role in fluid-filled tissues. In bone tissue, the external mechanical loading is transmitted to the cells by the movement of the interstitial fluid in the lacuna-canalicular system and by changes in the bone marrow pressure in trabecular bone. These forces influences bone cell fate, ultimately regulating skeletal adaptation to mechanical loading. In vitro studies have demonstrated that the application of native-like mechanical stimuli, such as fluid flow-induced shear stress and hydrostatic pressure, enhance bone cell proliferation and differentiation, although further research is needed to unravel the effects of cyclic pressure on bone tissue models. In this perspective, bioreactors represent a key technology for in vitro development and investigation of functional bone tissue models under defined and controlled stimuli.