Scientific research on the global carbon cycle has emerged as a high priority in biogeochemistry, climate studies, and global change policy. The emission of carbon dioxide (CO2) from fossil fuel combustion is a dominant driver of the current net carbon fluxes between the land, the oceans, and the atmosphere, and it is a key contributor to the rise in modern radiative forcing. Contrary to a commonly held perception, our quantitative knowledge about these emissions is insufficient to satisfy current scientific and policy needs. A more highly spatially and temporally resolved quantification of the social and economic drivers of fossil fuel combustion, and the resulting CO2 emissions, is essential to supporting scientific and policy progress. In this article, a new community of emissions researchers called the CO2 Fossil Fuel Emission Effort (CO2FFEE) outlines a research agenda to meet the need for improved fossil fuel CO2 emissions information and solicits comment from the scientific community and research agencies.