Myelofibrosis (MF) is the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In some patients with essential thrombocytopenia or polycythemia vera, which are relatively benign MPNs, MF develops as a natural evolution of their disease, resulting in post-essential thrombocythemia myelofibrosis (PET-MF) or post-polycythemia vera myelofibrosis (PPV-MF). Presenting with the same clinical features, including debilitating symptoms and signs of bone marrow failure, PET/PPV-MF has traditionally been considered akin to primary myelofibrosis (PMF). However, recent observations that PET/PPV-MF may be a distinct clinical entity from PMF have triggered efforts to improve prognostication in these diseases. Novel predictive models that incorporate rapidly emerging clinical and molecular data are being developed to improve outcomes in patients with PMF or PET/PPV-MF. This review focuses on the major clinical features and prognostic classification systems used in PMF and PET/PPV-MF.