With the widespread use of antimicrobial agents, the issue of microbial drug resistance has become increasingly severe, emerging as a major global public health challenge. Worldwide, there are significant differences in the types of drug-resistant bacteria, their epidemiological trends, and their resistance mechanisms. This article aims to review the current global status of microbial drug resistance, with a focus on the epidemiological trends, resistance mechanisms, and corresponding clinical treatment strategies for common drug-resistant bacteria and fungi, in order to provide a theoretical basis for promoting the rational use of antimicrobial agents.