Recurrent and second primary tumors arising within a previously radiated head and neck volume represent a difficult clinical scenario to manage. For patients who have resectable disease, surgery is the standard treatment. Chemotherapy is the standard for patients with unresectable or metastatic disease but offers no chance for cure. Re-irradiation (RRT) with concurrent chemotherapy is a potentially curative treatment option. In this article, we will review the basis for current chemoradiotherapy (CRT) regimens used in previously radiated patients, focusing on outcome and toxicity. Additionally, we will review radiotherapy techniques used in this setting and highlight the differences between definitive radiotherapy and RRT. Controversies, such as the utility of chemotherapy and RRT following surgical salvage, will be addressed. Finally, we will review investigations seeking to improve the therapeutic outcomes of patients treated with chemotherapy and RRT.