Acinetobacter baumannii is a significant concern in healthcare settings, particularly in critically ill patients, due to its ability to cause infections and develop resistance to multiple antimicrobial agents. The increasing prevalence of carbapenem-resistant A. baumannii (CRAB) has made it a critical public health and clinical priority, with high mortality rates and economic burdens. The bacterium's genetic adaptability and resistance mechanisms, such as β-lactamase production, target modification, reduced permeability, and biofilm formation, complicate treatment and management. Current therapies include sulbactam-based regimens, tigecycline, cefiderocol, and eravacycline, each with varying degrees of effectiveness and resistance profiles. Innovative approaches, such as novel β-lactam/beta-lactamase inhibitor combinations (BLICs) like sulbactam/durabactam, cefepime/zidebactam, imipenem/cilastatin/funobactam, and xeruborbaactam, show promise in overcoming resistance mechanisms. Phage therapy and other strategies, including LPS inhibitors and protein synthesis inhibitors, are also under investigation as potential alternatives. The fight against A. baumannii requires a coordinated, global response to develop new treatments and infection control strategies.Acinetobacter baumannii is a significant concern in healthcare settings, particularly in critically ill patients, due to its ability to cause infections and develop resistance to multiple antimicrobial agents. The increasing prevalence of carbapenem-resistant A. baumannii (CRAB) has made it a critical public health and clinical priority, with high mortality rates and economic burdens. The bacterium's genetic adaptability and resistance mechanisms, such as β-lactamase production, target modification, reduced permeability, and biofilm formation, complicate treatment and management. Current therapies include sulbactam-based regimens, tigecycline, cefiderocol, and eravacycline, each with varying degrees of effectiveness and resistance profiles. Innovative approaches, such as novel β-lactam/beta-lactamase inhibitor combinations (BLICs) like sulbactam/durabactam, cefepime/zidebactam, imipenem/cilastatin/funobactam, and xeruborbaactam, show promise in overcoming resistance mechanisms. Phage therapy and other strategies, including LPS inhibitors and protein synthesis inhibitors, are also under investigation as potential alternatives. The fight against A. baumannii requires a coordinated, global response to develop new treatments and infection control strategies.