As a nation, we underinvest in prevention and fail to implement strategies that ensure all population groups equitably share in the return on investment in prevention research and the benefits of prevention effectiveness. There is significant evidence indicating that by applying knowledge that we already have to reduce tobacco, inactivity, and obesity (known modifiable causes of cancer), we can prevent more than 50% of cancers. Vaccination against HPV, aspirin and selective estrogen receptor modulators, and screening programs further reduce risk. Evidence-based prevention strategies are inconsistently implemented across the United States. Substantial variation across States indicates that there is much room for improvement in implementation of prevention. Implementation science applies innovative approaches to identifying, understanding, and developing strategies for overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, tools, policies, and guidelines that will prevent cancer through application of evidence-based interventions. When we get implementation of prevention programs right and at scale, we achieve substantial population benefits. Although many efforts are underway to maximize our knowledge about the causes and treatments of cancer, we can achieve reductions in the cancer burden right now by doing what we already know. The time to start is now. .