In order to reduce the considerable usage of expensive but scarce platinum at the cathode in proton exchange membrane fuel cells (PEMFCs), it is necessary to pursue alternatives to platinum. The most promising platinum group metal (PGM)-free catalysts for oxygen reduction reaction (ORR) are atomically dispersed, and nitrogen-coordinated metal site catalysts denoted as M-N-C (M = Fe, Co, or Mn, etc.). Over the last few decades, there have been great advances in these catalysts with high ORR activity and promising initial fuel cell performance approaching traditional Pt/C catalysts. However, the stability of these highly active Fe-N-C catalysts under practical fuel cell conditions is still far from satisfactory. This review highlights recent advances in synthesizing efficient PGM-free catalysts for the ORR in PEMFCs, emphasizing our efforts on confinement strategies and spin state regulation methods. We also summarize several effective methods of improving mass and intrinsic activities. Furthermore, significant research efforts toward understanding the degradation mechanisms are made and the results are summarized, such as metal leaching, carbon corrosion, protonation, and micropore flooding. We also document several mitigation strategies to improve the lifetime of PGM-free catalysts, including controlling S1/S2 in Fe-N-C catalysts, using non-iron-based catalysts, enhancing metal-nitrogen bonds, improving the corrosion resistance of carbon carriers, and using buffered protonated liquids. Finally, the remaining challenges and possible solutions to the current atomic dispersion M-N-C catalyst are proposed in detail.