This chapter discusses chemoprevention of head and neck cancers, where tobacco smoke, alcohol and areca nut or betel nut are the major exposures associated with oral carcinogenesis. Alcohol has a synergistic effect when combined with tobacco smoke. Human papilloma virus (HPV) may play a role in oropharyngeal and oral carcinogenesis, where oral carcinogenesis is a multistep and multiyear process associated with the accumulation of genetic and phenotypic changes eventually leading to invasive cancer. Oral carcinogenesis is also a multifocal process that can affect all areas of the upper aerodigestive tract leading to multiple synchronous or metachronous lesions of the pharynx, larynx, esophagus and bronchus. Surrogate endpoint biomarkers are measurements of molecular changes in the target tissue that are purported to correlate with either the mechanism of action of the agent or anti-cancer effects.