Despite substantial contributions on the part of public, non-profit, and private sector organizations, the burden of cancer in the United States remains high. As public health organizations, particularly county, state, tribal, and territorial health departments, try to reduce the significant burden of cancer, they face additional issues that make it difficult to address cancer in a comprehensive way. These challenges along with the need to accelerate progress in reducing the U.S. cancer burden, prompted the Centers for Disease Control and Prevention (CDC) and its national partners to begin to work together to further define and describe comprehensive cancer control (CCC) as an approach to reducing the burden of cancer. CCC is defined as "an integrated and coordinated approach to reducing cancer incidence, morbidity, and mortality through prevention, early detection, treatment, rehabilitation, and palliation." This article describes the national effort to support comprehensive cancer control, outlines national and state level success in comprehensive cancer control, and provides a call to action to public, private, and non-profit organizations, governments of all levels, and individuals to renew their commitments to reducing the burden of cancer.