Proton exchange membrane fuel cells (PEMFCs) have received a sustained world-wide attention owing to their promising applications based on clean energy. However, their widespread applications are still restricted by the sluggish oxygen reduction reaction (ORR) process. Over the past decades, significant efforts have been devoted to developing efficient ORR catalysts, which have been summarized in numerous previous reviews. Unfortunately, most of them mainly focused on ORR activity on the rotating disk electrode (RDE) level, which cannot truly represent the performance in real applications. Developing and showcasing efficient catalysts evaluated at the membrane electrode assembly (MEA) level is of vital importance. In this review, we first briefly showcased the recent development of ORR catalysts and then put more emphasis on the discussion of designing efficient catalysts at MEA and full-cell level, aiming to help stimulate more attention on their practical applications.