Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm that is associated with a Janus kinase 2 (JAK2) mutation in most cases. The most recent update to the World Health Organization diagnostic criteria for PV was published in 2016. These were the modifications with the greatest effect: (1) lowering the hemoglobin threshold, allowing a diagnosis of PV at 16.5 g/dL in males and at 16.0 g/dL in females and (2) introducing a hematocrit cutoff (49% in males and 48% in females). Patients with PV who are older than 60 years or have had a previous thrombotic event are considered at high risk for thrombosis. Leukocytosis and a high allele burden are additional risk factors for thrombosis and myelofibrosis, respectively. After disease has progressed to post-polycythemia vera myelofibrosis (PPV-MF), survival must be assessed according to the recently developed Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM). This model is based on age at diagnosis, a hemoglobin level below 11 g/dL, a platelet count lower than 150 × 109/L, a percentage of circulating blasts of 3% or higher, a CALR-unmutated genotype, and the presence of constitutional symptoms. Therapy is based on phlebotomy to maintain the hematocrit below 45% and (if not contraindicated) aspirin. When a cytoreductive drug is necessary, hydroxyurea or interferon can be used as first-line therapy, although the demonstration of an advantage of interferon over hydroxyurea is still pending. In patients whose disease fails to respond to hydroxyurea, ruxolitinib is a safe and effective choice.