Anti-Human Leukocyte Antigen (HLA) donor specific antibodies (DSA) and anti-Angiotensin II Receptor Type 1 (AT1R) antibodies threaten short and long-term cardiac allograft survival. In this symposium we review the role of anti-HLA DSA and anti-AT1R antibodies in acute and chronic cardiac transplant antibody-mediated (AMR) rejection. We outline antibody-mediated allograft injury mechanisms, both complement dependent and independent, and describe HLA, other DSA and AT1R antibody detection, attributes and clinical correlates. We discuss the role of apheresis in AMR informed by one of the largest cardiac rejection cohorts in the United States. We hope to harness data from this evolving field to better manage antibody-mediated allograft rejection and to ultimately improve long-term allograft outcomes.