Modern risk-adapted treatment algorithm for myelofibrosis. The use of the dynamic international prognostic scoring system (DIPSS) and DIPSS-plus (DIPSS+) is the most comprehensive risk stratification tool currently available to guide therapeutic decision-making. The influence of driver mutation status as well the acquisition of additional somatic mutations may also prove to further refine this process. Ultimately, therapeutic approach is based on patient specific (age, performance status) and disease specific (symptom burden, presence of cytopenias) considerations in conjunction with an individual's personal goal of therapy. It should be stressed that whenever possible, clinical trial should be considered and hematopoietic stem cell transplantation remains the only potential curative treatment option available to a subset of patients. A indicates interferon-α; B, not FDA-approved for low-risk patients; C, second-generation JAK2 inh, combination therapy, imetelstat, PRM151, KB004, PF-04449913; D, HSCT on clinical trial when available; HU, hydroxyurea; RUX, ruxolitinib; and IMID, immunomodulator. *Erythropoiesis-stimulating agent can also be considered if baseline erythropoietin level is low.