Cure of locally advanced squamous cell carcinoma of the head and neck (SCCHN) is uncommon with radiotherapy alone. The desire for organ preservation in advanced resectable SCCHN and the need for better local therapy for unresectable disease have led to the development of treatment using radiotherapy and concurrent chemotherapy (RT/CCT). RT/CCT is an attractive strategy because the appropriate drug(s) may enhance radiation effects and independently contribute to local cytotoxicity. Concurrent treatment may combat tumor repopulation and provide the earliest possible treatment of distant micrometastases. RT/CCT may be integrated in synchronous or alternating schemes. Most randomized trials of RT/CCT versus radiation alone show superior local control, disease-free survival, and survival with combined modality treatment. Improved efficacy with RT/CCT is accompanied by increased acute toxicity, which necessitates compromises in the treatment design of most programs. Consequently the most effective RT/CCT regimen has not been defined. Chemical modifiers of toxicity are now under investigation in clinical trials and may allow for improved integration of RT/CCT.