Children living in the Commonwealth of Puerto Rico have the highest poverty and asthma prevalence rates of all U.S. children. Since 2000, a group of community, health care, education, housing, and academic representatives have been collaborating in a project to improve quality of life and reduce disparities among children with asthma in very poor communities in Puerto Rico. To date the project has implemented a successful intervention in the Luis Lloréns Torres Housing Project, aimed at adapting evidence-based interventions to improve the social and physical environment of children with asthma. The program has recently been extended to another San Juan housing area, the Manuel A. Pérez Housing Project. Using implementation theory, the authors report and reflect on the project’s experience to date, provide recommendations, and discuss implications of lessons learned to address inequities in asthma care throughout other underserved areas in the U.S., Latin America, and the Caribbean.