The Janus kinase 1 (JAK1) and JAK2 inhibitor ruxolitinib is currently the only therapy indicated for intermediate- or high-risk myelofibrosis. Results from clinical trials and experience in clinical practice have shown that ruxolitinib reduces myelofibrosis-related splenomegaly and symptom burden, and improves quality-of-life measures. In addition, ruxolitinib was associated with a survival advantage compared with placebo or conventional therapy in controlled trials. However, owing to the myelosuppressive effects of JAK2 inhibition, ruxolitinib is associated with decreases in hemoglobin and platelet counts, particularly during the first 8-12 weeks of therapy. Close monitoring of blood counts and careful dose management, particularly early in the course of therapy, are essential to avoid unnecessary cytopenias that may prompt premature treatment discontinuation by patients who otherwise would benefit from continued therapy. In general, starting doses and dose reductions should be used as recommended by the prescribing information based on platelet counts. A dose-escalation approach at the start of therapy is only recommended for patients with platelet counts of 50-100 x 10(9)/L. If possible, maximum tolerated doses should be maintained and extended treatment interruptions should be avoided to prevent lack or loss of treatment responses. An individualized dosing approach is key to long-term treatment success.