Decades of reading research have improved our understanding of the ways that young children learn how to read and of the component skills that support the ongoing development of reading and reading comprehension. However, while these investments have transformed reading instruction and reading outcomes for many learners, too many children are not reading at the basic level nor are they reading with understanding. The Institute of Education Sciences created the Reading for Understanding Research Initiative in 2010 to fund a set of connected projects that would enrich the theoretical frameworks that undergird efforts to improve deep comprehension and to design and test new interventions and assessments to improve reading for understanding across all grades in US schools. This article describes the central themes that guided the design of the Reading for Understanding Initiative and the work underway by the six research teams funded under this program.