Since its introduction to genome editing, CRISPR-Cas9 has been used to generate cell and animal models of disease, investigate relations between genomes and phenotypes, and interfere with disease development. Although most of its applications have been in basic research, efforts are underway to move CRISPR-Cas9 from bench to bedside. This review summarizes current and prospective applications of the CRISPR-Cas9 system in biomedical and translational research on solid tumors, as well as the challenges of expanding this technology into clinical use.