Head and neck cancer represents a paradigm for the prevention of environmentally induced diseases. Etiologic factors, including tobacco and alcohol, have been well established. Furthermore, disease development may depend not only upon such exposures but also upon a genetically defined susceptibility to exposure-induced DNA damage. As discussed in this review, the ability to identify etiologic factors, both external and host related, will lead to improved identification of individuals at risk. The development of novel strategies for cancer prevention will be promoted, among which lifestyle alteration will arguably play the most significant role. Therefore, this review places special emphasis on the translation of the understanding of disease into more effective behavioral modification strategies.