Proton exchange membrane water electrolyzers (PEMWEs) driven by renewable electricity provide a facile path toward green hydrogen production, which is critical for establishing a sustainable hydrogen society. The high working potential and the corrosive environment pose severe challenges for developing highly active and durable electrocatalysts for the oxygen evolution reaction (OER). To date, iridium (Ir)-based materials, largely metallic Ir and Ir-based oxides, are the most suitable OER electrocatalysts for PEMWEs due to their balanced activity and durability. Tremendous efforts have been devoted to improving the specific activity of Ir species to reduce the cost; however, advances in enhancing the durability of Ir-based electrocatalysts are rather limited. In this review, the recent research progress on tackling the stability issues of Ir-based OER electrocatalysts in acid media is summarized, aiming to provide inspiration for designing highly active and stable Ir-based electrocatalysts. The OER mechanism and the associated failure modes of active Ir species are summarized. Then, mechanistic studies on the dissolution behavior of Ir species and experimental attempts on enhancing the durability of Ir-based electrocatalysts are discussed. The personal perspectives for future studies on Ir-based OER electrocatalysts are also provided.