Clostridioides difficile genetics has rapidly advanced in recent years thanks to the development of tools for allelic replacement and transposon mutagenesis. In this Journal of Bacteriology issue, Müh et al extend the genetics toolbox by developing a CRISPRi strategy for gene silencing in C. difficile (U.Müh, A. G. Pannullo, D. S. Weiss, and C. D. Ellermeier, 2019, J Bacteriol 201:e00711-18. . https://doi.org/10.1128/JB.00711-18). The authors demonstrate the tunability and robustness of their CRISPRi system, highlight its utility in studying essential gene function, and discuss exciting new possibilities for dissecting C. difficile physiology.