Epithelial cancers in the lung and head and neck are a devastating group of diseases which account for approximately 35% of cancer deaths in the United States. Chemoprevention is a new strategy to block or reverse the carcinogenic process. Biological concepts including field carcinogenesis and multistep carcinogenesis strongly support the rationale for using chemopreventive approaches. Our group has focused on applications of translational retinoid studies to increase our knowledge of the molecular events in biology and chemoprevention. In this review, we will focus on four issues, biology, retinoids, retinoid clinical trials, and translational research, in the chemoprevention of aerodigestive cancers.