Prevention trials of whole foods or simple extracts offer prospects for reducing an expanding global burden of cancer effectively, and in contrast to promising isolated phytochemicals or pharmaceuticals, frugally. We use the term "green" chemoprevention to differentiate a food-centered approach that is sustainable in underserved populations. It can be applied to personalized medicine just as well as a pharmaceutical approach, but only green chemoprevention can be applied in both rich and poor settings. This MiniReview discusses some of the challenges of conducting food-based trials in developing countries, with particular emphasis on moving the limited number of promising phase II trials forward as placebo-controlled randomized trials, the gold standard for prevention studies. How does one define a placebo for a food? What is the regulatory context of such a food-based product? How can such products be produced and standardized to the benefit of a larger, individual trial, and importantly, the research community at large? What are the challenges and opportunities of conducting such trials in the international setting? Finally, how does one make the science practical?