Implementation science is a powerful framework, promoted by the WHO and the Global Fund, to adopt and integrate evidence-based health interventions and change practice patterns within specific settings. It takes into consideration specific characteristics of the setting, the intervention, and the individuals implementing the intervention to help understand why some interventions succeed while others fail. The framework is inherently multidisciplinary, incorporating qualitative and quantitative data, as well as cultural, political, and socioeconomic factors. We apply this framework to help understand successes and challenges encountered during two implementation efforts in the Dominican Republic: 1) Roll out of Community Health Clubs to improve water, sanitation and hygiene practices in rural Dominican communities, 2) Efforts to provide evidence to support the expansion of the Dominican national HIV treatment program to include treatment for those failing second-line medical treatment. The discussion highlights the importance of interventions that account for setting, including: inner setting including the need for buy-in within community-based organizations or clinic/providers implementing new programs, and outer setting, including governmental willingness to receive input from outsiders and the international funding environment. Characteristics of individuals involved in implementation that lead to success will be outlined: highly motivated, persuasive, persistent, and willing to prove long-term commitment to the project. Finally, we will emphasize the necessity of continuous process improvement, including early detection and correction of missteps for successful implementation.