The Global Fund raises and invests nearly US$4 billion a year to support programs run in more than 140 countries. The Global Fund strategy 2012–2016 is focused on “Investing for Impact”. In order to accomplish this, timely and accurate data are needed to inform strategies and prioritize activities to achieve greater coverage with quality services. Monitoring and evaluation is intrinsic to the Global Fund’s system of performance-based funding. The Global Fund invests in strengthening measurement and reporting of results at all stages of the grant cycle. The Global Fund approach to measurement is based on three key principles—(1) simplified reporting: the Global Fund has updated its measurement guidance to focus on impact, coverage and quality with the use of a harmonized set of indicators. (2) Supporting data systems—based on a common framework developed and supported by partners, it promotes investment in five common data systems: routine reporting including HMIS; Surveys—population based and risk group surveys; Analysis, reviews and transparency; Administrative and financial data sources; and, Vital registration systems. (3) Strengthen data use: the Global Fund funding encourages use of data at all levels—national, subnational and site level. Countries do not automatically prioritize M&E but when guidance, tools and investments are available, there is high level utilization of M&E systems in program design, planning, implementation, and results reporting. An in-depth analysis of the available data helps the Global Fund and countries to direct investments towards interventions where impact could be achieved and focus on target population groups and geographic areas that are most affected.