Solar-driven water-to-fuel conversion, analogous to natural photosynthesis, is an attractive energy conversion technology since it could provide an alternative to the current combustion of fossil fuels. Further understanding of catalysis in natural photosynthetics could benefit such technological developments. Photosynthetic organisms convert solar energy into NADPH and ATP (the biological fuels) through a process that is initiated at the oxygen evolving complex (OEC) of photosystem II (PSII). Such a catalytic site oxidizes water to generate the reducing equivalents for NADPH production and a pH gradient necessary for ATP biosynthesis. Water oxidation is a challenging four-electron reaction [2H2O → O2 + 4e- + 4H+] that is difficult to carry out efficiently in artificial photosynthetic systems. In this chapter, we review our recent studies of the OEC of PSII based on the recent X-ray diffraction model resolved at 1.9 Å resolution. We characterize the dark-adapted S1 state of the OEC and address the potential functional role of chloride during O2 evolution in PSII. These results are discussed in light of recent comparative studies on biomimetic oxomanganese complexes, revealing how Lewis base centers (such as carboxylate groups from the buffer solution, or surrounding environment) can play an important role as acid/base and redox cofactors in photosynthtetic water splitting. These findings have direct implications to catalytic water oxidation in photosystem II and provide useful information for the design of Mn-based biomimetic catalysts for artificial photosynthesis.