Chronic myelomonocytic leukemia (CMML) is a relatively uncommon hematologic malignancy that manifests as peripheral monocytosis, has varying degrees of bone marrow dysplasia, and is associated with poor outcomes. Despite a growing appreciation of the pathobiologic mechanisms driving CMML, current therapies have not clearly demonstrated any survival benefit. The complex pathobiology of CMML highlights the intricate aberrantly activated cellular pathways that influence disease phenotype and limit current treatment options. Understanding of these oncogenic pathways may provide novel mechanism-based treatment strategies that may ultimately offer better outcomes for patients. We reviewed the current diagnostic, prognostic, and molecular understandings, and we assessed the current and future treatment options for CMML.