Sex differences are increasingly recognized in the diagnosis and treatment of diseases. Biologically, the primary distinction between females and males is rooted in their sex chromosomes, XX in females and XY in males. While these chromosomal differences account for DNA-based variations, sex-related biological traits are complex and can be influenced by various factors, such as in sex-biased gene-regulatory networks and splicing events that contribute to phenotypic differences between sexes. Epigenetic modifications, such as DNA methylation and histone modification, further influence gene expression differently in females and males, affecting not only physiology but also disease susceptibility. Numerous studies suggest that sex differences also influence outcomes in patients with acute myeloid leukemia (AML). Here, we present the current evidence on sex differences across various aspects of AML.