Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. AML is a heterogeneous malignancy characterized by distinct genetic abnormalities. Recent discoveries have highlighted an additional important role of dysregulated epigenetic mechanisms in the pathogenesis of the disease. In contrast to genetic changes, epigenetic modifications are frequently reversible, which provides opportunities for targeted treatment using specific inhibitors. In this review, we will provide an overview of the current state of epigenetics and epigenetic therapy in AML and will describe perspectives on how to identify promising new approaches for epigenetic targeted treatment.