Over the last decades, we have witnessed a constant increase in infections caused by multi-drug-resistant strains in emergency departments. Despite the demonstrated effectiveness of antimicrobial stewardship programs in antibiotic consumption and minimizing multi-drug-resistant bacterium development, the characteristics of emergency departments pose a challenge to their implementation. The inclusion of rapid diagnostic tests, tracking microbiological results upon discharge, conducting audits with feedback, and implementing multimodal educational interventions have proven to be effective tools for optimizing antibiotic use in these units. Nevertheless, future multicenter studies are essential to determine the best way to proceed and measure outcomes in this scenario.