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CRISPR-Cas9 is a revolutionary genome-editing tool. Understanding how Cas9 recognizes DNA and how to control its function will be critical in improving the system. We used single-molecule FRET to elucidate a key validation step during DNA target recognition. We also used X-ray crystallography to show how a Cas9 inhibitor is able to permit DNA binding but prevent cleavage. Finally, CRISPR research is notable not just for the exciting applications, but also for its profound ethical implications.