Globally, each year 289,000 mothers die in childbirth and three million infants die in the first four weeks of life. The shortcomings in maternal and newborn health are particularly devastating in low-resource countries. This qualitative study describes the experience of an international nongovernmental organization, Jhpiego, which has been implementing public health programs to address maternal and newborn health outcomes for more than 40 years. Themes emerged from interviews with leaders of offices in a variety of countries with unique challenges related to health systems, human resources and infrastructure. Results emphasized the importance of partnerships with governments and international agencies for long-term program impact, as well as the recruitment of local talent for improving health systems to address problems that are best understood by the people who live and work in these countries. The discussion of program successes and challenges may inform best practices for promoting the health and wellness of women and families around the world.