The most threatening public health challenges today are chronic and complex and require joint effort from academic researchers in partnership with clinical and public health practitioners to identify and implement sustainable solutions that work in the real world. Practice-based research offers researchers and practitioners an underutilized way forward, an opportunity to work together to design and test feasible, evidence-based programs to address our greatest challenges. In this article, we outline the need for practice-based evidence, tools, and strategies that investigators can use to generate practice-based evidence, describe approaches to translating practice-based evidence into practice, and offer recommendations for making practice-based research the norm in public health.