Treatment of squamous cell carcinoma of the head and neck (SCCHN) has evolved greatly in the last two decades, owing to the integration of chemotherapy, advances in radiotherapeutic techniques, and organ-preserving surgery. Several randomized trials have established new standards of care that should be adopted. Current efforts are building on these earlier trials in order to improve survival and quality of life. Coincident with this, investigators are developing molecularly targeted approaches that hold promise for the future. This review will focus on current therapy for locally advanced, recurrent, and metastatic SCCHN and discuss controversies and directions for future research.