A new vision of science learning described in the "Next Generation Science Standards"--particularly the science and engineering practices and their integration with content--pose significant challenges for large-scale assessment. This article explores what might be learned from advances in large-scale science assessment and accountability systems, and in our understanding of students' engagement with the science and engineering practices, to inform such efforts. We highlight promising examples from current large-scale assessment programs, an alternative national accountability model, and cutting-edge research and offer several cautions to the field.