JAK inhibitors have been the go-to treatment for people with myelofibrosis (MF). Despite successfully reducing MPN-related symptoms, currently approved JAK inhibitors are not known to significantly change the course of MF disease. Similar to essential thrombocythemia (ET) and polycythemia vera (PV), therapy in these conditions focus primarily on lowering the risk of cardiovascular and thromboembolic consequences; in individuals with reduced thrombosis risks, careful waiting is frequently employed. The creation of rationally tailored medicines, however, with the aim of not only managing illness problems but also potentially altering disease course, has resulted from a greater understanding of MPN biology.