Recent strides in epidemiology (mutagen sensitivity assays) and basic molecular study of head and neck carcinogenesis are advancing chemoprevention in the head and neck. The clinical preventive activity of retinoids, the most studied and most active chemopreventive agents in this region, has been established in six randomized head and neck trials. Ongoing translational study of the p53 gene, nuclear retinoid receptors, and other cellular and molecular biomarkers will be necessary to achieve continuing progress in head and neck cancer chemoprevention.