In the last decade chemotherapy has gained widespread acceptance in the treatment of oral and pharyngeal cancer. Current standard treatment for advanced lesions consists of concomitant radiation and chemotherapy. This approach has provided marginal improvement of prognosis for Stage III-IV disease. Recent studies have explored the idea that locally delivered cytotoxic drugs could further improve prognosis in this patient population. We review this literature with the objective of popularizing these data and suggesting future directions for treatment and clinical research for head and neck cancer.