Fuel cells are highly efficient and green devices for direct chemical-to-electrical energy conversion. However, limited by slow kinetics of oxygen reduction reaction (ORR) in cathode, fuel cells require catalysts with noble metal like Pt, thus significantly increasing the cost of the fuel cells. Carbon-supported metal single atom catalysts (C-SACs) have excellent properties such as high atom utilization efficiency and selectivity. In addition, C-SACs show high ORR activity under different pH conditions, hence have been recognized as economical candidates to replace noble metal in fuel cells. This article reviewed the strategies used to improve ORR activity of C-SACs, including selecting different kinds of metal single atoms, tailoring coordination structure of metal centers, and heteroatomic doping to substrate. Performances of C-SACs in rotating disk electrode or battery device are also introduced. At last, the feasibility and potential challenges of C-SACs in practical application are prospected and summarized.