Heart transplantation is an excellent long-term treatment that confers functionality and longevity in select patients with end-stage heart failure. Yet, allograft rejection continues to pose a significant threat, especially in high-risk recipients and soon after transplantation. Of the two prevailing pathologic types of acute rejection in cardiac allografts, antibody-mediated rejection (AMR) had been variably defined and poorly understood for the past three decades when compared to cellular rejection. As a result, progress in understanding its pathologic and clinical behavior and the ability to find effective therapies had been hindered. Recent years have seen a renewed interest in cardiac AMR with efforts from pathologists, immunologists, and clinicians leading to a standardized diagnostic nomenclature.