Surgery remains the mainstay for nearly all tumors of the oral cavity. On the other hand, non-surgical approaches have shown equally effective tumor control and better functional outcomes in selected patients with tumors of the oropharynx. This is particularly true for human papillomavirus (HPV)-positive tumors. However, significant short-term toxicities and long-term functional sequelae result from definitive radiotherapy with chemotherapy for oropharyngeal carcinomas. Therefore, currently there are several clinical trials accruing patients for considering “de-intensification” of treatment for HPV-positive oropharynx cancers, with a resurgence of interest in surgical extirpation in selected patients. Until the results of these trials are available, surgery should be considered only in very selected patients with low-volume (T1, T2) primary tumors and low-volume (N0, N1, without extranodal extension [ENE]) nodal disease to avoid the addition of chemotherapy to postoperative radiation and thus reduce long-term functional sequelae of treatment.