The reconstruction of the whole orbitozygomatic framework (OZF) is complex and can be encountered in cases of congenital midface deformity, after tumor ablative surgery and in severe facial trauma. Nowadays, surgeon has a wide range of available techniques that have continually grown over the past years, optimizing the surgical management and the aesthetical outcomes. Among them, the autologous bone graft (ABG) remains one of the most suitable options : ABG is easy to harvest and has optimal biological properties for bone healing. It can be tailored to the patient anatomy thanks to the recent advances in computer-assisted surgery. However, substantial drawbacks remain such as the early resorption of the non-vascularized graft, the need of a donor site and its potential morbidity. Alloplastic reconstruction is another option that can resolve both the resorption issue and the donor site morbidity. Moreover, the 3D-printing technologies also allows the manufacturing of patient specific implants. However, alloplastic materials have a variable success, especially due to the high risk of infection or exposure. Consequently, regenerative medicine is a promising field that aims to find a procedure without the disadvantages of ABG or alloplastic based reconstructions, but displaying similar or even higher success rate. Indeed, recent tissue engineering strategies have demonstrated encouraging results for bone regeneration using natural or synthetic biomaterials, patient cells and synthetic bioactive substances. The objective of this review is to present the etiologies of OZF defect, the available reconstruction procedures as well as the current state of the research.