The complex shapes of skeletal components of the craniofacial region combined with the prominence of the face and paucity of overlying soft tissue create significant challenges for the reconstructive surgeon. The in vivo bioreactor strategy is a promising alternative to microvascular surgical techniques that combines tissue engineering principles with microvascular reconstructive techniques to create patient-specific, prevascularized bone flaps for reconstruction of complex maxillofacial defects. This article discusses the use of traditional vascularized bone flaps; preclinical studies using the in vivo bioreactor approach; case reports that have attempted this novel technique; and future challenges and considerations in the development of patient-specific, prevascularized bone flaps for maxillofacial reconstruction.