The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), which was launched in 2011, set a series of ambitious targets, including a reduction of new HIV infections among children by 90% by 2015 (from a baseline year of 2009) and AIDS-related maternal mortality by 50% by 2015. To reach these targets, the Global Plan called for unprecedented investments in the prevention of mother-to-child transmission of HIV (PMTCT), innovative new approaches to service delivery, immense collective effort on the programmatic and policy fronts, and importantly, a renewed focus on data collection and use. We provide an overview of major achievements in monitoring and evaluation across Global Plan countries and highlight key challenges and innovative country-driven solutions using PMTCT program data. Specifically, we describe the following: (1) Uganda's development and use of a weekly reporting system for PMTCT using short message service technology that facilitates real-time monitoring and programmatic adjustments throughout the transition to a “treat all” approach for pregnant and breastfeeding women living with HIV (Option B+); (2) Uganda's work to eliminate parallel reporting systems while strengthening the national electronic district health information system; and (3) how routine PMTCT program data in Nigeria can be used to estimate HIV prevalence at the local level and address a critical gap in local descriptive epidemiologic data to better target limited resources. We also identify several ongoing challenges in data collection, analysis, and use, and we suggest potential solutions.