Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative disorder that occurs during infancy and early childhood; this disorder is characterized by hypersensitivity of the myeloid progenitor cells to granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. JMML usually involves somatic and/or germline mutations in the genes of the RAS pathway, including PTPN11, NRAS, KRAS, NF1, and CBL, in the leukemic cells. Recently, additional genetic and/or epigenetic alterations have been identified in JMML, and these alterations appear to be prognostic indicators. Moreover, analyses of JMML stem cells and induced pluripotent stem cells (iPSCs) technology are expected to identify new targets for therapeutic interventions. Almost all patients with JMML experience an aggressive clinical course, and hematopoietic stem cell transplantation (HSCT) is the only curative treatment. The most suitable therapeutic regimen after diagnosis and the optimal conditioning regimen prior to HSCT have yet to be identified, though several clinical trials have been initiated worldwide. Taken together, these new findings indicate that genetic and/or epigenetic alteration-specific risk management may be introduced, and that suitable pre- or post-allogeneic HSCT treatments which are less toxic and can improve outcomes will be developed in the near future.