To achieve efficient and durable devices for spontaneous water splitting, it is necessary to overcome thermodynamic limitations on material stability, integrate catalysts with light absorbers, and engineer interfaces to reduce recombination loss. Central to this work is the discovery of new materials and methods, combined with the translational research required for their incorporation into prototypes. In our work, we use advanced x-ray and optical methods to understand the basic electronic structure, photocarrier dynamics, and chemical instabilities of existing semiconductor materials. This information allows for insights into the mechanisms of energy conversion and efficiency loss, as well as refinement of computational models for improved prediction of new semiconductors possessing desired band gaps, charge transport properties, and stabilities required for improved half-cell performance. Informed by these predictions, materials discovery efforts are aimed at synthesizing specific compositions for further investigation. These materials are typically compound thin film semiconductors, in which composition non-uniformities, structure, and morphology affect photoactivity. Probing these properties across different length scales, as well as their transformations in operational environments, allows for determination of chemical vulnerabilities and electronic deficiencies. Since these materials are typically characterized by poor intrinsic catalytic activity, it is generally necessary to integrate catalysts onto their surfaces. Process development and interface engineering are required to achieve desired catalyst composition and structure, while enabling efficient separation and transfer of photocarriers from semiconductor to catalyst. Since the performance of integrated systems is often governed by defect properties that are difficult to predict, combinatorial studies of catalyst/semiconductor assemblies are used to aid in the discovery of efficient interfaces. Finally, advances made at the half-cell level must be incorporated into prototypes capable of spontaneous overall water splitting and product separation, which impose strict requirements on operational conditions, light transmission paths, and physical scale. Key examples of research spanning material and mechanism discovery, development, and integration into prototypes will be given.