Abstract As estimated by the World Health Organization in its 2010 Global Status Report, for 2008, some 36 million of the 57 million deaths worldwide could be attributed to non-communicable chronic diseases, such as cardiovascular diseases and cancer. The emergence of cancer as a global health threat has been particularly challenging for less developed nations- two thirds of cancer deaths occur in low- and middle-income countries, where poor people with cancer tend to suffer more and die younger than in more developed countries. With the increasing age of the world population and its tendencies for tobacco use, decreasing physical activity, and poor dietary habits, the global epidemic of cancer will get substantially worse unless concerted and coordinated efforts by researchers, medical care providers, governments, and commercial entities can deliver rational and practical strategies for cancer prevention, detection, diagnosis, and treatment that are truly effective, and with refinement can become cost-effective. The AACR Frontiers in Cancer Prevention Conferences have attempted to bring together the broad collection of cancer research disciplines capable of contributing to the reduction of cancer and cancer mortality at a population scale, attracting experts in epidemiology, behavioral science, health services/economics, genetics, molecular biology, carcinogenesis, animal tumor modeling, imaging, clinical trials, and clinical care. Catalyzed in part by the Conferences, what started as increased dialog among these fields has started to yield productive scientific teams, with diverse members, poised to deliver solutions. Some of the teams have spontaneously organized around themes, such as infections and cancer, chronic or recurrent inflammatory processes and cancer, the epigenome as the genome record of life experience, etc., that have created a language and a logic that can transcend the perspectives of specific disciplines. Already, the power of technology drivers, including the progressive ease of genome-scale analyses and nearly vanishing costs of information storage and sharing, in support these teams has been balanced by significant limits, particularly in the consistent and quantitative collection of phenotypic and exposure data throughout the world. The promise and problems of cancer prevention will be considered using the example of prostate cancer, a growing global health problem encompassing all of the foundational disciplines of cancer prevention and control. Citation Format: William G. Nelson. Keynote Lecture: Global Initiatives in Cancer Prevention Research. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr OP-01.