On January 7, 2022, the University of Maryland Medical Center reported that the world’s first gene-edited pig heart was successfully transplanted into a 57-year-old man with end-stage heart disease, causing a global attention. The first gene-edited pig heart transplanted into a human successfully survived for 59 d without showing early signs of rejection, creating a history of xenotransplantation and marking a key step forward the clinical development of xenotransplantation. This article focuses on the role of gene editing in alleviating immune rejection, summarizes the case of xenotransplantation at the Maryland Medical Center, and outlines the current status of xenotransplantation and the unresolved issues of xenotransplantation. It is expected that xenotransplantation can successfully enter the clinic in the near future.