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Identifying women living with HIV, initiating them on lifelong antiretroviral treatment (ART), and retaining them in care are among the important challenges facing this generation of health care managers and public health researchers. Implementation research attempts to solve a wide range of implementation problems by trying to understand and work within real-world conditions to find solutions that have a measureable impact on the outcomes of interest. Implementation research is distinct from clinical research in many ways yet demands similar standards of conceptual thinking and discipline to generate robust evidence that can be, to some extent, generalized to inform policy and service delivery. In 2011, the World Health Organization (WHO), with funding from Global Affairs Canada, began support to 6 implementation research projects in Malawi, Nigeria, and Zimbabwe. All focused on evaluating approaches for improving rates of retention in care among pregnant women and mothers living with HIV and ensuring their continuation of ART. This reflected the priority given by ministries of health, program implementers, and researchers in each country to the importance of women living with HIV returning to health facilities for routine care, adherence to ART, and improved health outcomes. Five of the studies were cluster randomized controlled trials, and 1 adopted a matched cohort design. Here, we summarize some of the main findings and key lessons learned. We also consider some of the broader implications, remaining knowledge gaps, and how implementation research is integral to, and essential for, global guideline development and to inform HIV/AIDS strategies.