Summary The impact of donor specific HLA antibodies (DSA) on solid organ transplant outcomes has been recognised for over half a century. This article reviews the mechanisms of DSA formation, details the laboratory methods for detecting DSA, discusses the clinical and histological manifestations of DSA in the allograft and explores the options for management of DSA. The challenges posed by pre‐existing and de novo DSA are explored with current therapeutic strategies described. A method for stratifying the risk associated with pre‐existing DSA is explained and the importance of understanding immunological risk associated with transplantation to facilitate optimal personalised decision making for transplant recipients is highlighted. Future directions for further managing the risk associated with DSA are proposed.