Abstract In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating “big data” science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits. Cancer Epidemiol Biomarkers Prev; 22(4); 508–16. ©2013 AACR.