Historically, patients with unresectable head and neck cancer have been treated with definitive radiation therapy alone. In recent years, numerous trials have assessed the role of concurrent chemoradiation for these patients. Many of the larger, more recent trials are summarized here, with particular emphasis on the effect of combined therapy on survival and toxicity. Most of the trials have demonstrated modest benefit or a trend toward benefit in survival, progression-free survival, or local control in patients treated with concurrent chemoradiation. However, nearly every trial also showed increased toxicity with the more aggressive regimens. Two meta-analyses also show a small but significant improvement in survival and increased toxicity from a concurrent treatment approach. Therefore, patients should be well selected by their physicians to be able to tolerate the side effects of combined-modality therapy and must be well informed of the pros and cons of concurrent chemoradiation during the decision-making process.