The role of chemotherapy in the management of patients with head and neck carcinoma is actively being investigated. Currently, chemotherapy is considered the standard of care for patients with recurrent or metastatic disease. Several single-agent and combination regimens have been used, demonstrating a partial response rate of 30% or less. The role of chemotherapy in the neo-adjuvant and adjuvant setting is less clearly defined. Concomitant chemoradiotherapy and rapid sequence alternating combined therapy have demonstrated a survival advantage in randomized trials. The degree of toxicities associated with these regimens, however, currently limits their use to clinical trials. Biologic therapy has been evaluated neo-adjuvantly and in recurrent and metastatic disease. Additional trials are needed before definitive conclusions can be made regarding its effectiveness and indications. The role of chemoprevention is rapidly expanding, with new agents and combinations currently in clinical trials.