African Americans have a substantially increased mortality rate compared to Whites in many cancers, including breast and cervix. The Deep South Network for Cancer Control (the Network) was established to develop sustainable community infrastructure to promote cancer awareness, enhance participation of African Americans and other special populations in clinical trials, recruit and train minority investigators, and develop and test innovative community-based cancer control measures to eliminate cancer mortality disparities in special populations. This article describes the steps necessary to form the network and the process and activities required to establish it as an effective infrastructure for eliminating disparities between Whites and African Americans in the United States.