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Rational drug design that leverages routine, high-resolution protein structure determination is driving the discovery and development of diverse biologic and small molecule therapies. The rapid maturation of cryo-electron microscopy (cryo-EM) over the past decade underpins the dramatic expansion of modalities benefitting from structural information. Cryo-EM delivers rapid, atomic-scale epitope mapping for antibody therapeutics and immune response profiling, supports the elucidation of mechanisms of action, and expands the range of therapeutic targets accessible to structure-based drug design.