Chronic myelomonocytic leukemia is a clonal malignancy of the ageing hematopoietic stem cell characterized by a biased differentiation leading to persistent monocytosis and inconstant hypersensitivity of myeloid progenitors to granulo-monocyte colony-stimulating factor (GM-CSF). Cytogenetic abnormalities identified in 30-40 % of patients and gene mutations detected in every patient can be used to stratify patients into risk groups that guide the therapeutic choices. TET2, SRSF2, ASXL1, and genes of the Ras pathway are the most frequently mutated genes, with ASXL1 mutations negatively affecting the disease outcome. Allogeneic stem cell transplantation is the first option to consider, especially in younger patients with poor prognostic factors. There is no firm clinical guideline in transplant-ineligible patients, but hypomethylating agents might be an interesting option. A consensus prognostic scoring system and specific response criteria are now required to facilitate the evaluation of new therapeutic strategies in clinical trials specifically dedicated to this disease.