The article discusses a new perspective on the role of hydrogen binding energy in single-atom catalysts (SACs) for improving hydrogen-based technologies. It challenges the conventional belief that HBE is the primary factor in designing SACs and highlights the limitations it poses on enhancing catalytic activity, particularly in the hydrogen evolution reaction (HER). The study, published in Angewandte Chemie International Edition, emphasizes the importance of pushing the boundaries of metal site designs to optimize HER by addressing poisoning effects and considering factors like realistic H* adsorption strengths and potential HER activity at coordinating N-sites. Researchers found that revising metal-nitrogen-carbon designs can lead to more efficient catalysts by avoiding poisoning effects caused by hydroxyl radical (HO*) and oxygen radical (O*). By utilizing models that incorporate HBE calculations under realistic adsorption conditions, they can accurately predict HER activity. Additionally, the study introduces new descriptors, combining HBE and Gibbs free energy, to provide guidelines for developing advanced SACs and breaking conventional limitations. The research team's work aims to resolve debates on HER descriptors and propel catalyst design forward. By developing an advanced model to overcome HO poisoning limitations, they intend to create novel single- and dual-atom catalysts suitable for various pH conditions, particularly in alkaline environments. The Hao Li Lab's Digital Catalysis Platform hosts a vast experimental catalyst database, offering insights into the study's data and computational structures.