The prognosis of acute myeloid leukemia (AML) remains unsatisfactory. Among the reasons for the poor response to therapy and high incidence of relapse, there is tumor cell immune escape, as AML blasts can negatively influence various components of the immune system, mostly weakening T-cells. Since leukemic cells can dysregulate immune checkpoints (ICs), receptor-based signal transductors that lead to the negative regulation of T-cells and, eventually, to immune surveillance escape, the inhibition of ICs is a promising therapeutic strategy and has led to the development of so-called immune checkpoint inhibitors (ICIs). ICIs, in combination with conventional chemotherapy, hypomethylating agents or targeted therapies, are being increasingly tested in cases of AML, but the results reported are often conflicting. Here, we review the main issues concerning the immune system in AML, the main pathways leading to immune escape and the results obtained from clinical trials of ICIs, alone or in combination, in newly diagnosed or relapsed/refractory AML.