Polycythemia vera is the most common of the myeloproliferative neoplasms characterized by elevated hematocrit, splenomegaly and increased thrombotic risk. Together these conditions result in significant symptom burden and a reduced quality of life for these patients. The recent identification of genetic variants associated with polycythemia vera have enhanced methods for classification and diagnosis of disease, contributed to more robust risk stratification models and led to the identification of novel targeted therapies for treatment of disease and alleviation of symptom burden. As these advances have the potential to provide significant benefits to patient quality of life and clinical outcomes, clinical challenges pertaining to incorporation of these new methodologies and therapies into everyday clinical practice are coming to light. Therefore, it is imperative that healthcare professionals are kept current of new and emerging clinically relevant findings and how their utilization in the clinical setting can provide optimal care for patients with PV for the enhancement of quality of life and clinical outcomes.