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The treatment options for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) have substantially improved over the last 5 years. However, even though novel targeted agents (e.g. venetoclax, IDH1/2 and novel FLT-3 inhibitors; cytosolic isocitrate dehydrogenase 1/2 and fms-like tyrosine kinase 3 inhibitor) and improved chemotherapeutics (e.g. CPX-351; liposomale Daunorubicin/Cytarabine) are entering clinics, physicians are still confronted with high relapse and treatment failure rates. Thus, novel new strategies are required to improve AML therapy. Application of genetically engineered T cells (i.e. chimeric antigen receptor T cells, CAR-T cells) has proven to be highly effective in B cell-derived neoplasia and early data suggest also a high potential in the treatment of AML. This short review highlights the current approaches but also limitations of CAR-T cell therapy in AML precluding their current routine clinical use. Among a plethora of problems to be overcome, a critical issue will be to find relatively selective actionable targets in AML.