Platinum (Pt)-based catalysts have been unanimously considered the most efficient catalysts for the oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs). Unfortunately, the exorbitant cost of Pt hampers the widespread adoption and development of PEMFCs. Scientists have devoted tremendous efforts to achieving higher catalytic activity with less Pt usage by constructing delicate nanostructures. Substituting Pt with cheaper metals may be a feasible solution but suffers from a relatively low intrinsic activity. Recently, single-atom catalysts (SACs), which possess the highest metal utilization and excellent activity because of the minimum size of metal and unique coordination structure, are developing rapidly and have been regarded as a potential alternative to Pt-based materials. Here, we review the development of conventional Pt- and nonprecious-metal-based ORR catalysts and summarize recent achievement in SACs for the ORR. A brief perspective on the remaining challenges and future directions of SACs is also presented. Display omitted Proton-exchange membrane fuel cells (PEMFCs) are now of great interest because of zero emission and high efficiency. Current PEMFCs require an unaffordable amount of Pt-based catalysts to overcome the sluggish kinetics of the oxygen reduction reation (ORR) on cathodes, hampering the widespread adoption of PEMFCs. Tremendous efforts have been devoted to achieving higher catalytic activity with less Pt usage by nanoscale engineering. Substituting Pt with cheaper metals may be also a feasible solution but suffers from low intrinsic activity. Recently, single-atom catalysts (SACs), which possess the highest metal utilization and excellent activity because of the minimum size of metal and unique coordination structure, have been regarded as potential alternatives. Here, we review the development of Pt- and nonprecious-metal-based ORR nanocatalysts and summarize recent achievements in SACs for the ORR. At last, a brief perspective on the remaining challenges and future directions of SACs for the ORR is presented. Proton-exchange membrane fuel cells (PEMFCs) are considered the ideal devices for direct chemical-to-electrical energy conversion but suffer from the sluggish kinetics of the oxygen reduction reaction (ORR) on cathodes. For an overview of the recent progress in this field, this review introduces the mechanism and electrochemical evaluation of the ORR, elaborates on the development of conventional Pt- and nonprecious-metal-based catalysts for the ORR, summarizes recent achievements in the ORR, and presents the remaining challenges as well as future directions of single-atom catalysts.