Locally recurrent head and neck malignancies after definitive radiation or chemoradiation represent challenging clinical scenarios requiring careful consideration of individualized risks and benefits before deciding upon the next best course of therapy. Herein, a case-based approach to personalized decision making highlights the expert opinions of leaders in head and neck oncology. Topics of interest include optimal candidacy for reirradiation or salvage surgical resection, the judicious use of chemotherapy as induction therapy or as a radiosensitizing agent, the incorporation of immunotherapy into the treatment paradigm for locally recurrent disease, and the impact of various treatment modalities on quality of life and functional outcomes. Interestingly, the lack of consensus among the experts on topics as fundamental as the appropriateness of offering reirradiation at all and as nuanced as target volume delineation for the reirradiated field suggests that there is no straightforward approach in this scenario. Common to all opinions is a desire to maximize the therapeutic ratio for a patient potentially facing a grim prognosis, and honest discussions about goals of care and expectations for post-treatment quality of life should be central to the clinical approach to this and similar cases. (C) 2020 Published by Elsevier Inc.