PURPOSE OF REVIEW: This review highlights recent progress in applying genome editing to the study and treatment of cardiovascular disease (CVD). RECENT FINDINGS: Recent work has shown that genome editing can be used to determine the pathogenicity of variants of unknown significance in patient-derived induced pluripotent stem cells. These cells can also be used to test therapeutic genome editing approaches in a personalized manner. Somatic genome editing holds great promise for the treatment of CVD, and important proof of concept experiments have already been performed in animal models. Here we briefly review recent progress in patient-derived cells, as well as the development of somatic genome-editing therapies for CVD, with a particular focus on liver and heart. SUMMARY: Translating this technology into the clinic will require precise editing enzymes, efficient delivery systems, and mitigation of off-target events and immune responses. Further development of these technologies will improve diagnostics and enable permanent correction of some of the most severe forms of CVD.