Beta-lactam (β-lactam) drugs are the most widely used antimicrobial agents globally, with significant variations in practice of skin test across different countries. In 2021, China issued relevant guidelines, aiming to promote a transition of skin test mode from routine screening to evidence-based evaluation, but challenges still remain in practical implementation. This review systematically analyzes the practical differences in skin test for β-lactam drugs through comparing domestic and international guidelines and research, exploring the underlying scientific, cultural, and institutional factors, with the aim of providing reference for the implementation of policies and the optimization of antimicrobial stewardship strategies in China.