The field of after-school programming for youth has grown substantially in the past 25 years, theoretically, methodologically, and practically. With increasingly sophisticated developmental lenses (e.g., positive youth development) and methods (e.g., mixed methods, advanced growth modeling techniques), we are now at a point where the field is ready for more and better integration of research and practice. We present an overview of both what is known and what the field needs to address to optimize program opportunities to best serve all youth. We focus on three major areas: (a) understanding what after-school programs do; (b) how we study after-school programs, and; (c) what we do with the resulting evidence. We argue that researchers, practitioners and policy makers must hone conceptual models, constructs and measures, evaluation designs, and practical and theoretical questions about after school programming to provide information that is useful in determining not only whether particular programs are helping youth, but also how they are helping and how they could help more.