Myelodysplastic syndrome (MDS) is a bone marrow (BM) failure syndrome characterized by loss of cellularity, differentiation blockade, and increased risk of progression to acute myeloid leukemia (AML). Inflammation is a hallmark of cancer and can affect the composition of the tumor’s immune microenvironment and response to treatment. In blood cancers, driver mutations associated with MDS and AML were shown to have pro-inflammatory effects, and inflammation associated with the accumulation of these mutations can contribute to pathogenic conditions. In MDS, the BM microenvironment is characterized by high levels of inflammation, consisting of increased levels of inflammatory cytokines and alteration of the BM niche. However, the exact role of inflammation in mediating MDS progression remains unknown. We have recently characterized the role of inflammation in remodeling the immune microenvironment in AML. We identified dysfunctional immune populations associated with inflammation, including inhibitory B and T cell subsets. Analysis of a transcriptomic dataset of MDS patients revealed similar populations in the BM of MDS patients, as well as an increase in inflammation levels as patients progress to AML. Therefore, we hypothesize that increased inflammation plays an important role in MDS progression, and targeting inflammation or inflammation-associated immune populations may provide an efficient therapeutic strategy for MDS.