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Proton exchange membrane water electrolyzers (PEMWEs) are a key technology for large-scale green hydrogen production, yet further improvements in efficiency, durability, and cost are needed for widespread deployment. While major progress has been achieved through advances in electrocatalyst development, particularly for iridium-based oxygen evolution catalysts, increasing evidence shows that performance limitations at low loadings originate from interfacial losses rather than intrinsic catalytic activity alone. In this Perspective, we argue that PEM water electrolysis has entered an interface-dominated regime, in which membranes, catalyst layers, and porous transport layers (PTLs) must be designed as a coupled materials system. Focusing on the anode side of PEMWEs, we review recent developments in membrane architectures for gas crossover mitigation and chemical stability, catalyst layer microstructural engineering for low iridium loadings, and titanium-based PTL designs that improve interfacial contact and catalyst utilization. By comparing catalyst-coated membrane (CCM) architectures with emerging porous transport electrode (PTE) concepts, we show that many reported performance gains arise from redistribution, rather than elimination, of interfacial resistance within the membrane electrode assembly. Based on these insights, we outline how an interface-driven co-design framework can guide the development of efficient, durable, and low-iridium PEM water electrolyzers.