The management of patients with locally and/or regionally advanced head and neck squamous cell carcinoma (HNSCC) has evolved from purely surgical to a multidisciplinary effort that includes radiation and chemotherapy. Randomized trials and meta-analyses have led to widespread acceptance of organ preservation strategies with the combination of cytotoxic chemotherapy and radiation therapy (1–3). Single-modality or multimodality treatments are typically employed for early-stage and locoregionally advanced disease, respectively. For patients with unresectable, recurrent or metastatic disease, systemic therapy has shown efficacy in numerous well-designed clinical trials.