Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, highlighting the high socioeconomic impact. Current treatment strategies like compound-based drugs or surgeries are often limited. On the one hand, systemic administration of substances is frequently associated with adverse side effects; on the other hand, they typically provide only short-time effects requiring daily intake. Thus, new therapeutic approaches and concepts are urgently needed. The advent of CRISPR-Cas9 genome editing offers great promise for the correction of disease-causing hereditary mutations. As such mutations are often very rare, gene editing strategies to correct them are not broadly applicable to many patients. Notably, there is recent evidence that gene editing technology can also be deployed to disrupt common pathogenic signaling cascades in a targeted, specific, and efficient manner, which offers a more generalizable approach. However, several challenges remain to be addressed ranging from the optimization of the editing strategy itself to a suitable delivery strategy up to potential immune responses to the editing components. This review article discusses important CRISPR-Cas9-based gene editing approaches with their advantages and drawbacks and outlines opportunities in their application for treatment of cardiovascular diseases.