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The Next Generation Science Standards will require large-scale professional development (PD) for all science teachers. Existing research on effective teacher PD suggests factors that are associated with substantial changes in teacher knowledge and practice, as well as students’ science achievement. But the complexity of the U.S. educational system continues to thwart the search for a straightforward answer to the question of how to support teachers. Interventions that take a systemic approach to reform hold promise for improving PD effectiveness.