Now, more than ever, there is great need for personalized cancer prevention. We define personalized cancer prevention as a strategy that will enable each person to reduce his or her risk for lethal cancer by matching the dose, duration, and timing of an intervention with their own cancer risk profile. Most research studies provide us with data on the average person. But who is the average person anyway? The central tenet of personalized cancer prevention is that average is overrated. In this article, we frame what are the major obstacles to developing personalized cancer-reducing interventions: the lack of validated, non-invasive stratifiers of risk; the U-shaped dose response between cancer-fighting nutrients (e.g., selenium) and DNA damage, meaning that more of a good thing is not necessarily a good thing; the relatively brief duration of interventions evaluated in human prevention trials; the challenge of finding populations in which the impact of early life interventions on the incidence of cancers affecting older adults can be studied; and the interindividual differences in gene expression that may influence a person's response to a particular nutrient. Moreover, we contend that those who study personalized cancer prevention will need a unique constellation of expertise, including an understanding of cancer and aging, a passion for prevention, and proven health communication skills. We propose that becoming cross-trained in cancer and aging and taking more responsibility for communicating health-related research to the public in the proper context are two of the most important ways scientists can move us all closer to the goal of personalized cancer prevention. Every fisherman knows that where he casts his net determines his catch. Now, we ask: When it comes to solving the cancer problem, where should we be casting our nets?