Proton exchange membrane fuel cells (PEMFCs) are leading candidates in utilizing clean energy resources for application in transportation, stationary, and portable devices. In PEMFCs, cathode catalysts are crucial for overall performance and durability due to kinetically slow oxygen reduction reactions (ORR). Because platinum (Pt), a state-of-the-art ORR catalyst, is rare and expensive, the development of high-performance platinum metal group (PGM)-free catalysts is highly desirable for future fuel cell technologies. Among various PGM-free catalyst formulations, metal and nitrogen co-doped carbon (M-N-C, M: Fe, Co, or Mn) catalysts have exhibited encouraging activity and stability in acidic media for the ORR, which possess great potential to replace Pt in the future. Therefore, based on our extensive experience in the field of ORR catalysis, the talk will comprehensively summarize the basic principles in the design and synthesis of M-N-C catalysts for durable, inexpensive, and high-performance PEMFCs with an emphasis on Co- and Mn-N-C catalysts to avoid Fenton reactions between Fe2+ and H2O2, which can generate free radicals and lead to the degradation of catalysts, ionomers, and membranes in PEMFCs. Furthermore, template-free 3D hydrocarbon frameworks as attractive precursors to advanced M-N-C catalysts will be discussed to enhance intrinsic ORR activities in acidic media significantly. Also, the long-term performance durability of M-N-C cathodes will be discussed extensively to provide potential solutions to enhance catalyst stability in PEMFCs. Finally, this talk will provide an overall perspective on the progress, challenges, and solutions of PGM-free catalysts for future PEMFC technologies.