During oxygenic photosynthesis, the oxidation of water to molecular oxygen and a proton is catalysed by the enzyme Photosystem II (PSII). The reaction takes place at a CaMn4 cluster that is found within the PSII protein matrix, shielded from the external environment. It has been proposed that dedicated channels and pathways exist in the protein complex for the passage of the substrate and product molecules to and from this active site. In this chapter, the rationales for the possible existence of such pathways are considered, and the various biochemical, spectroscopic and computational studies for identifying their possible locations and functions are reviewed. The different approaches and techniques employed and their influences on the respective results and conclusions are also compared and discussed.