In 1998, the National Research Council published People and Pixels: Linking Remote Sensing and Social Science. The volume focused on emerging research linking changes in human populations and land use/land cover to shed light on issues of sustainability, human livelihoods, and conservation, and led to practical innovations in agricultural planning, hazard impact analysis, and drought monitoring. Since then, new research opportunities have emerged thanks to the growing variety of remotely sensed data sources, an increasing array of georeferenced social science data, including data from mobile devices, and access to powerful computation cyberinfrastructure. In this article, we outline the key extensions of the People and Pixels foundation since 1998 and highlight several breakthroughs in research on human–environment interactions. We also identify pressing research problems—disaster, famine, drought, war, poverty, climate change—and explore how interdisciplinary approaches integrating people and pixels are being used to address them.