Squamous cell carcinomas of the oropharynx account for approximately 25% of all head and neck squamous cell malignancies. Most patients present with locally advanced tumors and require a multimodality approach to treatment, with input from qualified surgeons and radiation and medical oncologists. For organ preservation, concurrent chemoradiotherapy is usually preferred over surgery with adjuvant radiotherapy. Controversies regarding management of particular populations of locally advanced oropharyngeal tumors exist, including whether to include induction chemotherapy before chemoradiation, the use of biologic agents as radiation sensitizers, and how best to manage the neck after definitive treatment. Additionally, infection with human papilloma virus (HPV), particularly HPV-16, is now an established risk factor for head and neck cancer. Most cases involve the oropharynx, and prognosis seems to be much better than for patients with non–HPV- and tobacco-related tumors. Given the distinct differences between these HPV and non–HPV-related cancers, controversy also exists regarding the management of these patient populations, with the concern that HPV-related malignancies may be overtreated. Unfortunately, these and other questions concerning the management of locally advanced oropharyngeal cancers are outstanding. Hence, it is critical that eligible patients are screened for and encouraged to participate in clinical trials.