During the past 4 years, the first molecular markers for polycythemia vera (PV) have been described. These markers include decreased expression of the thrombopoietin receptor c-Mpl, increased expression of the surface receptor polycythemia rubra vera-I, and insulin-like growth factor-I hypersensitivity. Characterization of these abnormalities has allowed the development of the first molecular diagnostic tools for PV. However, despite these advances, the molecular mechanisms leading to the development of PV remain poorly understood. This review summarizes and evaluates recent advances in our understanding of molecular aberrations in PV.