This Reprint brings together cutting-edge contributions that address the acute and evolving challenge of antimicrobial resistance in the intensive care setting. Critically ill patients in Intensive Care Units (ICUs) face a disproportionate burden of infections caused by multidrug-resistant organisms, demanding a rigorous appraisal of both epidemiological trends and therapeutic strategies. In this collection we highlight three interconnected domains: (1) the dynamic epidemiology of key pathogens in ICUs, including Gram-negative bacilli, non-fermenters, and other high-risk bacteria; (2) advances in microbiological diagnostics-encompassing rapid molecular methods, phenotypic detection, and real-time therapeutic guidance techniques; and (3) optimization of antimicrobial therapy grounded in pharmacokinetics/pharmacodynamics, novel agents, and stewardship frameworks tailored to the critical-care environment. The aim is to offer clinicians, microbiologists, and researchers a coherent resource that merges mechanistic insights with practical treatment algorithms for complex resistance mechanisms. By integrating surveillance data, therapeutic case series, and reviews of emerging antimicrobials, this Reprint supports evidence-based decision-making and fosters interdisciplinary collaboration in the fight against antimicrobial resistance in intensive care.