Introduction: Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm that is associated with debilitating constitutional symptoms, progressive splenomegaly, and cytopenias. Ruxolitinib, a JAK1/2 inhibitor, is currently the only drug approved for the treatment of patients with intermediate or high risk MF. There is rationale and even limited clinical data supporting the use of ruxolitinib in lower risk patients, although this has not yet been validated in a randomized controlled trial.Areas covered: We examine rationale for using ruxolitinib in lower risk MF patients, including survival data from COMFORT-I and COMFORT-II, specific patient populations that may derive clinical benefit, and the future impact of molecular analysis on risk stratification and treatment. Additionally, we consider the potential risks associated with earlier intervention with ruxolitinib therapy.Expert commentary: Although there exists rationale for the use of JAK2 inhibitor therapy in lower risk MF patients, we eagerly await the results of an ongoing randomized controlled trial addressing this question before recommending wider use in the community setting.