摘要:SummaryCryo-electron tomography has stepped fully into the spotlight. Enthusiasm is high. Fortunately for us, this is an exciting time to be a cryotomographer, but there is still a way to go before declaring victory. Despite its potential, cryo-electron tomography possesses many inherent challenges. How do we image through thick cell samples, and possibly even tissue? How do we identify a protein of interest amidst the noisy, crowded environment of the cytoplasm? How do we target specific moments of a dynamic cellular process for tomographic imaging? In this review, we cover the history of cryo-electron tomography and how it came to be, roughly speaking, as well as the many approaches that have been developed to overcome its intrinsic limitations.Graphical abstractTimeline of major cryo-EM milestones discussed in the text. Citations for each event are as follows: (1) (1979): ; (2) (2004): ; (3) (2007): ; (4) (2008): NA; (5) (2012): and ; (6) (2014/VPP): ; (7) (2014/cryo-PALM): ; (8) (2018): ; (9) (2019): ; (10) (2017): .Display OmittedBiochemistry; Cell biology; Structural biology