Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm that is mainly characterised by reactive bone marrow fibrosis, extramedullary haematopoiesis, anaemia, hepatosplenomegaly, constitutional symptoms, leukaemic progression, and shortened survival. As such, this malignancy is still orphan of curative treatments; indeed, the only treatment that has a clearly demonstrated impact on disease progression is allogeneic haematopoietic stem cell transplantation, but only a minority of patients are eligible for such intensive therapy. However, more recently, the discovery of JAK2 mutations has also led to the development of small-molecule JAK1/2 inhibitors, the first of which, ruxolitinib, has been approved for the treatment of MF in the United States and Europe. In this article, we report on old and new therapeutic strategies that proved effective in early preclinical and clinical trials, and subsequently in the daily clinical practice, for patients with MF, particularly concerning the topics of anaemia, splenomegaly, iron overload, and allogeneic stem cell transplantation.