Oral and pharyngeal cancers are among the leading cancer sites. Surgery, radiation, chemotherapy, or combination therapies are common treatment modalities. Radiotherapy and chemotherapy cause significant morbidity and long-term irreversible sequelae in the oral cavity. Surgical resection can be mutilating, disfiguring, and deeply affect self-image. Orofacial defects have unique limitations and challenges for both the surgeon and the maxillofacial prosthodontist. Microvascular surgical techniques and the use of osseointegrated implants improve the rehabilitation potential of the various head and neck defects. This article reviews current treatment modalities of tumor therapy, their consequences, and the restoration of maxillofacial defects.