biostudies-literatureRobertson MJNINDS NIH HHSNational Institutes of HealthNIGMS NIH HHS124-135https://www.ebi.ac.uk/biostudies/studies/S-EPMC8760134biostudies-literatureUnknown47(2)Structure-based drug discovery (SBDD) is an indispensable approach for the design and optimization of new therapeutic agents. Here, we highlight the rapid progress that has turned cryo-electron microscopy (cryoEM) into an exceptional SBDD tool, and the wealth of new structural information it is providing for high-value pharmacological targets. We review key advantages of a technique that directly images vitrified biomolecules without the need for crystallization; both in terms of a broader array of systems that can be studied and the different forms of information it can provide, including heterogeneity and dynamics. We discuss near- and far-future developments, working in concert towards achieving the resolution and throughput necessary for cryoEM to make a widespread impact on the SBDD pipeline.Trends in biochemical sciencesDrug discovery in the era of cryo-electron microscopy.PMC8760134R01 NS092695R01 NS122394T32 GM089626Skiniotis GMeyerowitz JGRobertson MJfalseDrug discovery in the era of cryo-electron microscopy.Structure-based drug discovery (SBDD) is an indispensable approach for the design and optimization of new therapeutic agents. Here, we highlight the rapid progress that has turned cryo-electron microscopy (cryoEM) into an exceptional SBDD tool, and the wealth of new structural information it is providing for high-value pharmacological targets. We review key advantages of a technique that directly images vitrified biomolecules without the need for crystallization; both in terms of a broader array of systems that can be studied and the different forms of information it can provide, including heterogeneity and dynamics. We discuss near- and far-future developments, working in concert towards achieving the resolution and throughput necessary for cryoEM to make a widespread impact on the SBDD pipeline.2022-01-01T00:00:00Z2022 Feb2025-04-19T14:19:46.417Z2025-02-19T04:45:58.078ZS-EPMC87601343428179110.1016/j.tibs.2021.06.008