NF-κB usually has antiapotptic effects and is involved in regulation of cell proliferation and intercellular communication. This is also true for the malignant cells in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS), including the malignant stem cells. However, both AML and MDS patients are heterogeneous with regard to the effect of pharmacological NF-κB inhibition, and the final effect will probably also depend on the pharmacological agent used for the inhibition, e.g. proteasomal inhibitiors versus specific inhibitors. Even though initial studies suggest that NF-κB inhibitors have antileukemic effects, their future clinical use will also depend on their toxicity profile.