A substantial amount of research effort has been directed toward the development of Pt-based catalysts with higher performance and durability than conventional polycrystalline Pt nanoparticles to achieve high-power and innovative energy conversion systems. Currently, attention has been paid toward expanding the electrochemically active surface area (ECSA) of catalysts and increase their intrinsic activity in the oxygen reduction reaction (ORR). However, despite innumerable efforts having been carried out to explore this possibility, most of these achievements have focused on the rotating disk electrode (RDE) in half-cells, and relatively few results have been adaptable to membrane electrode assemblies (MEAs) in full-cells, which is the actual operating condition of fuel cells. Thus, it is uncertain whether these advanced catalysts can be used as a substitute in practical fuel cell applications, and an improvement in the catalytic performance in real-life fuel cells is still necessary. Therefore, from a more practical and industrial point of view, the goal of this review is to compare the ORR catalyst performance and durability in half- and full-cells, providing a differentiated approach to the durability concerns in half- and full-cells, and share new perspectives for strategic designs used to induce additional performance in full-cell devices.