Myelofibrosis (MF) is a classical Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal proliferation of pluripotent stem cells, dysfunctional kinase signaling, and abnormal cytokine release. MF is a heterogeneous disease, ranging from asymptomatic to being associated with one or more of the following problems: profound anemia, splenomegaly, constitutional issues, and even rapid progression to overt leukemia. Recently, important progress has been made. A Janus kinase (JAK) 2 mutation affects both pathogenesis and prognosis. Conventional treatment is primarily palliative and has only limited effects on the natural course of the disease. Allogeneic stem cell transplantation is the only curative treatment, but is presently limited to eligible intermediate-2 and high-risk patients. Ruxolitinib, the first drug approved by the Food and Drug Administration for treatment of intermediate-2 and high-risk patients, is currently the best available therapy for symptomatic MF patients. Additional JAK inhibitors are under investigation. Emerging therapies include immunomodulators and inhibitors of histone deacetylase (HDAC), mammalian target of rapamycin (mTOR), and telomerase. A better understanding of disease pathogenesis will lead to the development of better treatments modifying the disease course and, ultimately, curing the condition. (Korean J Med 2016;90:293-297)