As the development of polymer electrolyte membrane fuel cells (PEMFCs) has sped up in recent years, producing active and durable electrocatalysts has become an increasingly important technical challenge. Platinum–cobalt (Pt–Co) alloy electrocatalyst has been commercially applied to hydrogen-powered fuel cell vehicles, and their intermetallic forms promise better durability, which is crucial to satisfy the 8000 h lifetime target of heavy-duty vehicles and other transportation options. In this feature article, we first present the atomically ordered structures of Pt–Co intermetallic, then discuss the thermodynamic and kinetic driving forces for making the PtCo-based intermetallic nanoparticles with desired structural attributes, followed by recent examples to illustrate how to achieve better control in composition, size, and shape. Discussion on the relationship between the key structural features and catalytic performance is focused on the application of Pt–Co intermetallic nanostructures as oxygen reduction reaction (ORR) electrocatalysts for hydrogen-powered PEMFCs. We emphasize specifically the importance of intermetallic structures for enhancing the durability and summarize the characterizations of their electrocatalytic performance in both three-electrode system and full cell studies. Finally, we provide our perspectives on the design, synthesis, characterization, and property studies of Pt–Co intermetallic nanoparticles as ORR electrocatalysts. This article should provide a new understanding on the design of ORR electrocatalytic applications using this class of intermetallics.