© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The electrochemical CO2 reduction reaction (CO2RR) is of great importance to tackle the rising CO2 concentration in the atmosphere. The CO2RR can be driven by renewable energy sources, producing precious chemicals and fuels, with the implementation of this process largely relying on the development of low-cost and efficient electrocatalysts. Recently, a range of heterogeneous and potentially low-cost single-atom catalysts (SACs) containing non-precious metals coordinated to earth-abundant elements have emerged as promising candidates for the CO2RR. Unfortunately, the real catalytically active centers and the key factors that govern the catalytic performance of these SACs remain ambiguous. Here, this ambiguity is addressed by developing a fundamental understanding of the CO2RR-to-CO process on SACs, as CO accounts for the major product from CO2RR on SACs. The reaction mechanism, the rate-determining steps, and the key factors that control the activity and selectivity are analyzed from both experimental and theoretical studies. Then, the synthesis, characterization, and the CO2RR performance of SACs are discussed. Finally, the challenges and future pathways are highlighted in the hope of guiding the design of the SACs to promote and understand the CO2RR on SACs.