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A large and ever-expanding set of CRISPR-Cas systems now enables the rapid and flexible manipulation of genomes in both targeted and large-scale experiments. Numerous software tools and analytical methods have been developed for the design and analysis of CRISPR-Cas experiments, including resources to design optimal guide RNAs for various modes of manipulation and to analyze the results of such experiments. A major recent focus has been the development of comprehensive tools for use on data from large-scale CRISPR-based genetic screens. As this field continues to progress, a clear ongoing challenge is not only to innovate, but to actively maintain and improve existing tools so that researchers across disciplines can rely on a stable set of excellent computational resources for CRISPR-Cas experiments.