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The Merck Childhood Asthma Network (MCAN) initiative selected five sites (New York City, Puerto Rico, Chicago, Los Angeles, and Philadelphia) to engage in translational research to adapt evidence-based interventions (EBIs) to improve childhood asthma outcomes. The authors summarize the sites' experience by describing criteria defining the fidelity of translation, community contextual factors serving as barriers or enablers to fidelity, types of adaptation conducted, and strategies used to balance contextual factors and fidelity in developing a "best fit" for EBIs in the community. A conceptual model captures important structural and process-related factors and helps frame lessons learned. Site implementers and intervention developers reached consensus on qualitative rankings of the levels of fidelity of implementation for each of the EBI core components: low fidelity, adaptation (major vs. minor), or high fidelity. MCAN sites were successful in adapting core EBI components based on their understanding of structural and other contextual barriers and enhancers in their communities. Although the sites varied regarding both the EBI components they implemented and their respective levels of fidelity, all sites observed improvement in asthma outcomes. Our collective experiences of adapting and implementing asthma EBIs highlight many of the factors affecting translation of evidenced-based approaches to chronic disease management in real community settings.