Risk of cancer in sub-Saharan Africa is linked to demographic shifts, urbanization, changing lifestyle, preventable oncogenic infections including the HIV/AIDS pandemic. Of the 12.4 million incident cancer cases for 2008, more than half will occur in developing countries accounting for two-thirds of the estimated global cancer deaths. In Africa, low levels of awareness, poverty, limited budgets and poor health care systems complicate cancer prevention, and treatment. Coordinated response by international agencies, NGOs and national governments targeting education, training, cancer control and management are a priority along with good quality clinical and laboratory practice, accessible and affordable chemotherapy, and treatment programs designed for low resource environments. Effective utilization of existing treatment and prevention strategies will decrease cancer mortality in Africa by more than 50% and implementation science research to evaluate challenges in deploying these strategies is urgently needed. There are unique opportunities for gaining novel insights about cancer etiology and biology by conducting studies in Africa to exploit the diversity of genomic and environmental factors and their interaction, an opportunity not replicable in other environments and populations. The African genome is the most heterogeneous with high frequency of mutations and short Haplotype lengths; its geography includes most of the world's flora and fauna; it is home to diverse culture with different social, economic and cultural characteristics and its biodiversity is yet to be adequately systematically exploited for phyto-pharmaceuticals. Heightened international collaborative such as the Human Heredity and Health in Africa project (H3Africa) co-sponsored by NIH and the Wellcome Trust explore role of genomic factors and their interaction with a range of environmental factors and are model for other collaborative ventures to unlock new therapies based on natural products drug discovery and new etiologic agents.