Chronic myelomonocytic leukemia is a heterogeneous hematologic malignancy classified among the mixed myelodysplastic/myeloproliferative diseases by the World Health Organization because of its myelodysplastic and myeloproliferative characteristics. In the proliferative form, diagnosis should include screening for known molecular abnormalities associated with constitutively active tyrosine kinases, which may be candidates for targeted therapies. Because patient life expectancy is highly variable and there is no consensus on optimal therapy, clinicians are advised to rely on a specific risk-oriented scoring system for clinical decision-making for individual patients. Although supportive care represents the milestone for disease management, novel active agents such as hypomethylating drugs recently have become available, so that the current therapeutic armamentarium now includes different treatment alternatives. Allogeneic stem cell transplantation may represent a curative option in highly selected patients.