Oxygenic photosynthesis is the primary solar energy-conversion process that supports much of life on Earth. It is initiated by photosystem II (PSII), an enzyme that extracts electrons from H2O and feeds them into an electron-transport chain to result in chemical synthesis using the input of solar energy. PSII can be immobilized onto electrodes for photoelectrochemical studies, in which electrons photogenerated from PSII are harnessed for enzyme characterization, and to drive fuel-forming reactions by electrochemically coupling the PSII to a suitable (bio)catalyst. Research in PSII photoelectrochemistry has recently made substantial strides in electrode design and unravelling charge-transfer pathways at the bio–material interface. In turn, these efforts have opened up possibilities in the field of bio-photoelectrochemistry, expanding the range of biocatalysts that can be systematically interrogated, including biofilms of whole photosynthetic cells. Furthermore, these studies have accelerated the development of semi-artificial photosynthesis to afford autonomous, solar-driven, fuel-forming biohybrid devices. This Review summarizes the latest advancements in PSII photoelectrochemistry with respect to electrode design and understanding of the bio-material interface, on both the protein and cellular level. We also discuss the role of biological photosynthetic systems in present and future semi-artificial photosynthesis.