Although the incidence of significant rejection post-heart transplant (HTx) has decreased in time, over 10% of patients continue to have an episode of treated rejection in the first year after an HTx. This chapter provides a comprehensive overview of acute cellular, antibody-mediated, mixed, and biopsy-negative rejection. It also addresses the management of hyperacute rejection and late rejection. The treatment landscape for HTx rejection will continue to evolve and improve and will require further research to reduce the risk of long-term complications and improve clinical outcomes.