Organometallic Ir precatalysts have been found to yield homogeneous Ir-based water-oxidation catalysts (WOCs) with very high activity. The Cp*Ir catalyst series can operate under a variety of regimes: it can either act as a homogeneous or a heterogeneous catalyst; it can be driven by chemical, photochemical, or electrochemical methods; and the molecular catalyst can either act in solution or supported as a molecular unit on a variety of solid oxides. In addition to optimizing the various reaction conditions, work has continued to elucidate the catalyst activation mechanism and identify water-oxidation intermediates. This Perspective will describe the development of the Cp*Ir series, their many forms as WOCs, and their ongoing characterization.