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Rational design leveraging routine, high resolution protein structure determination is driving the discovery and development of diverse biologic and small molecule therapies. Since the “Resolution Revolution” almost one decade ago, the rapid maturation of cryo-electron microscopy (cryo-EM) underpins the dramatic expansion of modalities benefitting from structural information. Cryo-EM delivers rapid epitope mapping on the atomic scale for antibody therapeutics and immune response profiling, supports elucidation of mechanism of action and is also enabling more therapeutic targets than ever before for Structure-Based Drug Design.