An efficient homogeneous catalytic system for the visible-light-induced production of hydrogen from water utilizing cyclometalated iridium(III) and tris-2,2'-bipyridyl rhodium(III) complexes is described. Synthetic modification of the photosensitizer Ir(C boolean AND N)(2)(N boolean AND N)(+) and water reduction catalyst Rh(N boolean AND N)(3)(3+) creates a family of catalysts with diverse photophysical and electrochemical properties. Parallel screening of the various catalyst combinations and photoreaction conditions allows the rapid development of an optimized photocatalytic system that achieves over 5000 turnovers with quantum yields (1/2 H-2 per photon absorbed) greater than 34%. Photophysical and electrochemical characterization of the optimized system reveals that the reductive quenching pathway provides the necessary driving force for the formation of [Rh(N boolean AND N)(2)](0), the active catalytic species for the reduction of water to produce hydrogen. Tests for system poisoning with mercury or CS2 provide strong evidence that the system is a true homogeneous system for photocatalytic hydrogen production.