Introduction: Ruxolitinib is a potent and selective JAK1/JAK2 inhibitor that has shown superiority as compared to available conventional chemotherapies, in terms of reduction in splenomegaly and improvement of symptoms and quality of life.Areas covered: Data published about overall survival in the major randomized sponsored trials and in independent series of patients were detailed. Indeed, data regarding action of ruxolitinib on allele burden reduction and potential activity of the drug on pathogenetic mechanisms involved in increased fibrosis has been reviewed.Expert commentary: Data extrapolated from clinical trials demonstrated an advantage of survival when the drug was compared to placebo or to best available therapy. Moreover, in the long-term, JAK2 allele burden was reduced during treatment and about 50% of patients achieved improvement or stabilization of fibrosis. For this latter activity, several pathways have been involved. In conclusion, ruxolitinib is able to modify the natural outcome of patients affected by myelofibrosis, independently from its nature, both in primary and secondary diseases.