This work focuses on the use of revascularized free flaps for the reconstruction of the major defects of the mandible after the removal of advanced-stage tumors in irradiated patients. It uses three representative cases to study the problems of complex patients and the possible reconstructive options. The cases, all three young patients (two females and one male), had undergone a mandibulectomy and adjuvant radiotherapy for malignant neoplasms. In each case, secondary reconstruction of the mandible and soft tissue was necessary and was performed using microvascular free flaps. An osteomyocutaneous iliac crest free flap was used in two cases, whereas a double flap (fibula free flap + rectus abdominis free flap) was used in the other case. In all three cases, after the microvascular reconstruction, an orthognathic procedure was performed to obtain the correct maxillomandibular relationship. The advantages and disadvantages of the various techniques used are discussed.