The Merck Childhood Asthma Network (MCAN) used evidence-based interventions (EBIs) for children with asthma to design community-based programs in a wide variety of settings—with varying resource constraints and priorities—that were often determined by the program context. Although challenges were faced, lessons learned strongly suggest that adapting and implementing EBIs is feasible in a variety of settings using a multisite approach. Lessons learned during the MCAN initiative presented unique opportunities to refine best practices that proved to be important to translation of EBIs in community-based settings. The adopted best practices were based on experiential learning during different phases of the project cycle, including monitoring and evaluation, translational research, and implementing policies in local program environments. Throughout this discussion it is important to note the importance of program context in determining the effectiveness of the interventions, opportunities to scale them, their affordability, and the ability to sustain them. Lessons learned from this effort will be important not only to advance science-based approaches to manage childhood asthma but also to assist in closing the gap between intervention development (discovery) and program dissemination and implementation (delivery).