The AIDS pandemic had a significant impact in Puerto Rico, especially among the heterosexual populations, in particular women. Women are one of the fastest growing risk groups with HIV/AIDS in the USA and constitute about half of the AIDS cases in the world. During the past 10 years Puerto Rico has ranked among the top 5 jurisdictions in the United States in AIDS cases rates, among men, women and children. In 1987 a universal prenatal HIV screening program was implemented in the University Hospital catchment area consisting of approximately 5,000 deliveries per year. Because of the early identification of pregnant women living with HIV, access to lifesaving clinical research and the implementation of multiple strategies and comprehensive care, the perinatal HIV transmission has been reduced to zero since 1997, with a blip of one case in 2002, and none since then. The availability and access to clinical and behavioral research has been one of the key elements for this success story. The programs involved and responsible for this spectacular outcome, namely the Maternal Infant Studies Center (CEMI-Spanish Acronym) and Gamma Projects at the University of Puerto Rico School of Medicine are described. The cost savings impact of stopping mother-infant perinatal HIV-1 transmission has been calculated to be approximately $34 to $58 million dollars in 10 years. The impact of the effectiveness of these programs in having healthy uninfected infants, prolonging and improving the quality of life of those living with HIV, and providing hope to families affected by this epidemic is incalculable.