In the current review, we mainly focus on PD-1/PD-L1 dysregulation in MDS/AML, including the following aspects: (1) the pattern of aberrant PD-1/PD-L1 expression in MDS/AML; (2) the mechanisms by which dysregulated PD-1/PD-L1 signaling influences the BM microenvironment; (3) the mechanisms by which abnormal inflammatory signaling, genetic and/or epigenetic alterations and interactions between cells regulate PD-1/PD-L1 expression; (4) the mechanisms by which drugs, including hypomethylating agents (HMAs), affect PD-1 expression in MDS/AML. Here, PDCD1 is linked to acute myeloid leukemia.