PURPOSE OF REVIEWThe purpose of this article is to discuss the rationale of targeting CD123 using chimeric antigen receptor (CAR) T cells for the treatment of leukemia. RECENT FINDINGSCD123 is a leukemia-associated antigen that expresses at high levels in leukemic stem cells and leukemic blasts and low level in normal hematopoietic stem/progenitor cells. Immune-based therapies targeting CD123 are being developed. Preclinical data suggest that CD123 CAR T cells exhibit potent antileukemic activity and various impacts on normal hematopoiesis. SUMMARYCD123 is an attractive surface target for novel antileukemic therapies. CD123 CAR T-cell-based immunotherapy is a promising treatment for patients with relapsed or refractory acute myeloid leukemia.