An estimated one in five Americans is functionally illiterate; they lack the literacy skills to access information or to perform many other basic tasks vital to their health and well-being. The National Cancer Institute and its Cancer Information Service have been working since 1990 to develop cancer-education strategies and materials to reach people with limited literacy skills. This paper reviews the link between cancer and illiteracy, the magnitude of the problem, and the association between cancer, certain health-related behaviors, and educational attainment. It also examines innovative National Cancer Institute and Cancer Information Service programs and materials designed to reach this high-risk population.