Abstract: Proton exchange membrane (PEM) fuel cells have gained increasing interest from academia and industry, due to its remarkable advantages including high efficiency, high energy density, high power density, and fast refueling, also because of the urgent demand for clean and renewable energy. One of the biggest challenges for PEM fuel cell technology is the high cost, attributed to the use of precious platinum group metals (PGM), e.g., Pt, particularly at cathodes where sluggish oxygen reduction reaction takes place. Two primary ways have been paved to address this cost challenge: one named low-loading PGM-based catalysts and another one is non-precious metal-based or PGM-free catalysts. Particularly for the PGM-free catalysts, tremendous efforts have been made to improve the performance and durability—milestones have been achieved in the corresponding PEM fuel cells. Even though the current status is still far from meeting the expectations. More efforts are thus required to further research and develop the desired PGM-free catalysts for cathodes in PEM fuel cells. Herein, this paper discusses the most recent progress of PGM-free catalysts and their applications in the practical membrane electrolyte assembly and PEM fuel cells. The most promising directions for future research and development are pointed out in terms of enhancing the intrinsic activity, reducing the degradation, as well as the study at the level of fuel cell stacks.