Ruxolitinib is an orally available, ATP-competitive inhibitor, selective for tyrosine-protein kinases JAK1 and JAK2 and is the most advanced JAK1/JAK2 inhibitor in development for the treatment of myeloproliferative neoplasms. The suggested mechanism of action of ruxolitinib is attenuation of cytokine signaling via the inhibition of JAK1 and JAK2 (wild-type or mutated forms), resulting in antiproliferative and proapoptotic effects. In the phase III COMFORT-I trial conducted in patients with myelofibrosis, ruxolitinib demonstrated durable reductions in splenomegaly. The proportion of patients that achieved spleen volume reduction ≥ 35% from baseline to 24 weeks was 41.9 % with ruxolitinib versus 0.7% with placebo (P < 0.0001), as evaluated by magnetic resonance imaging or computed tomography. In the phase III COMFORT-II trial, reductions in spleen volume ≥ 35% were observed in 31.9% of patients treated with ruxolitinib versus 0% with best available therapy at week 24, and 28.5% versus 0% at week 48 (both P < 0.0001). Low toxicity, alleviation of constitutional symptoms, weight gain and improvement in general physical condition were observed with ruxolitinib treatment which may substantially improve quality of life in patients with myelofibrosis.