Besides outlining the varied genome-editing approaches that are now available for use, this Review focuses on the gene for which, by far, the most proof-of-concept studies have been reported — PCSK9, a regulator of blood cholesterol levels and driver of coronary heart disease risk — with the goal of illustrating for the reader the various ways in which the field is advancing the development of genome-editing therapies for cardiovascular diseases. The gene discussed is PCSK9; the disease is coronary artery disorder.