Rubin Mesa MD, Serge Verstovsek MD, Richard Silver MD, and Emily Knight R.N., O.C.N. offer their perspectives and insights for optimal management of PV after hydroxyurea (HU) failure. HU is frequently used for first-line cytoreductive therapy in patients with PV, but some patients are poorly served, experiencing inadequate disease or symptom control, intolerable toxicity, or both, and may benefit from switching to a different therapy.