Human leukocyte antigen (HLA) sensitization is a common problem in patients being assessed for organ transplantation. Two overarching principles that must be adhered to when evaluating approaches to sensitized patients are: (1) ensuring equitable access for potential recipients to transplantable organs; and (2) maintaining optimal long-term patient and graft outcomes post-transplant. Approaches increasingly used to manage sensitized heart transplant candidates are crossmatching (virtual [VXM], based on comparison of donor HLA to recipient antibody specificities, or prospective real-time [XM]) to avoid donor-specific antibodies, or desensitization to reduce the amount of antibodies that are present. We propose that the best strategy for management of highly sensitized patients awaiting heart transplantation is combining mechanical circulatory support as a bridge to a (-) VXM or XM together with adoption of a national prioritized sharing algorithm for highly sensitized patients.