Purpose of Review <p>The purpose of this review article is to provide a comprehensive overview of xenotransplantation, including historical background, current state of the field, and future directions.</p> Recent Findings <p>In 2021, a team from NYU successfully transplanted a porcine kidney into a brain-dead recipient, with the xenograft maintaining function for the entirety of the 54-hour trial period. This was followed by several additional successful trials, culminating in 2022 with the successful transplantation of a cardiac xenograft from a 10-gene-edited pig into a human recipient with end-stage cardiomyopathy. In 2023, the same team repeated their success, with a second patient surviving for several weeks after cardiac xenotransplantation. Concurrently, a team from Massachusetts General Hospital achieved another breakthrough with the successful transplantation of a porcine kidney into a human recipient with end-stage renal disease, with the graft functioning until the patient died from other causes roughly two months later. Several exciting clinical trials are currently ongoing.</p> Summary <p>The field of xenotransplantation has fundamentally evolved, from a theoretical concept marred by seemingly insurmountable hurdles, to a rapidly advancing reality that has already achieved clinical success. Progress has been driven by advances in in tissue engineering, immunology, and organ preservation. While long-term graft viability has yet to be achieved, it is likely that xenotransplantation will continue to improve and play a major role clinically moving forward. Here, we summarize the history, current status, and future directions of xenotransplantation.</p>