Head and neck cancers are a heterogeneous group of diseases involving the oral cavity, pharyngeal tube, and larynx. Given the drug therapy options available, clinical pharmacists can play an important role in the care of this patient population. They can recommend a regimen based on efficacy, toxicity, and patient-specific factors; ensure that the prescribed regimen has been studied and reported in the literature; verify dosages; and monitor and counsel patients about adverse effects. Chemotherapy plus radiation (chemoradiation) is often the standard treatment for patients with stage III or nonmetastatic stage IV head and neck cancer. Cisplatin-based regimens are preferred, although carboplatin may be appropriate in some circumstances. Induction therapy with a docetaxel-based regimen is recommended for some patients; however, this therapy has been associated with a high frequency of grade 3 and 4 neutropenia and febrile neutropenia. Cetuximab, an epidermal growth factor receptor inhibitor, is the newest agent approved for treatment of head and neck cancer. Although evidence supports cetuximab combined with cisplatin versus cisplatin alone for patients with metastatic disease, the role of combination therapy is less clear in patients undergoing chemoradiation. Patients with head and neck cancer may experience swallowing difficulties or mouth pain, possibly interfering with drug administration and adherence; thus, pharmacists in all practice settings should be knowledgeable about different regimens and alternative routes of administration. Xerostomia and mucositis are common adverse effects of radiation therapy, and it is critical that good oral hygiene practices are maintained. Patients may achieve symptomatic relief from xerostomia with saliva substitutes, and clinical experience suggests that use of pilocarpine is worthwhile. Until more evidence becomes available, prevention of xerostomia and mucositis with amifostine is still controversial. Salt-water rinses, bioadherent oral gel, and honey are relatively inexpensive and nontoxic agents for managing mucositis. Because of the expense of palifermin, it is best reserved for refractory cases. Skin toxicities are common with radiation. Rash is also a common adverse effect of cetuximab. When used together, they may produce complicated skin toxicities. It is important to become familiar with the grading of these rashes so that appropriate therapy can be recommended. As pharmacotherapy for head and neck cancers continues to evolve, clinical pharmacists will continue to have an important role in optimizing treatment for patients by balancing efficacy and toxicity.