Ruxolitinib is a potent JAK1/JAK2 inhibitor that has shown superiority over conventional therapies for the treatment of MF. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression. On November 16, 2011, the U. S. Food and Drug Administration approved ruxolitinib for the treatment of intermediate and high risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Recently, in two phase III COMFORT studies, ruxolitinib demonstrated rapid and durable reductions in splenomegaly, improved MF-related symptoms and quality of life, and prolonged survival compared with placebo and best available therapy (BAT). The primary and key secondary endpoints were both met: the proportion of patients achieving a response (defined as a ≥35% reduction in spleen volume) at week 48 (ruxolitinib, 28.5%; BAT, 0%; P< .0001) and week 24. But the median duration of spleen response has not yet been reached. And the rates of AEs of special interest (anemia, thrombocytopenia, bleeding, and infections) generally decreased after the first 24 weeks of treatment with ruxolitinib. Few new or worsening decreases in hemoglobin levels and platelet counts were observed with longer exposure to ruxolitinib.