Despite progress in surgical and reconstructive techniques, as well as advances in radiotherapy delivery methods, a significant proportion of patients irradiated for head-and-neck cancer develop locoregional recurrence. These patients are also at high risk of developing new second primary cancers of the head and neck. Because of the heterogeneity of this population with respect to disease-related and patient-related factors, such as previous treatment, tumor recurrence site, disease extent, and performance status, the optimal treatment of locoregionally recurrent or second primary cancers of the head and neck remains to be defined. Although surgical resection typically constitutes the mainstay of treatment, effective salvage therapy is often precluded by anatomic inaccessibility and the risk of perioperative complications. Although chemotherapy alone has traditionally been considered an alternative to surgery, the response rates have been poor, with nearly all patients dying of disease progression within months. Similarly, salvage therapy using re-irradiation has historically been avoided because of concerns regarding toxicity. Although the results of more recent studies using contemporary treatment techniques and conformal delivery methods have been somewhat more promising, the role of re-irradiation after previous full-course radiotherapy is still considered investigational by many. Numerous questions remain unanswered, and practical guidelines for clinical decision-making are sparse.