The treatment of Acinetobacter baumannii (A. baumannii) infections remains a significant challenge due to its high antimicrobial resistance, particularly to beta-lactams, quinolones, aminoglycosides, and tetracyclines. A. baumannii is a major cause of nosocomial infections, especially in critically ill patients, and has been associated with severe outcomes, including high mortality rates. The bacterium's resistance profile includes resistance to carbapenems and colistin, making it difficult to treat. Recent studies highlight the importance of using effective antibiotics such as sulbactam, polymyxins (colistin and polymyxin B), tigecycline, and aminoglycosides for multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Cefiderocol has also emerged as a useful option in the treatment of these infections. Sulbactam, a beta-lactamase inhibitor, has shown clinical effectiveness against A. baumannii, particularly when used in combination with ampicillin. High-dose sulbactam (6–9 g/day) has been associated with lower mortality compared to comparator regimens. The combination of sulbactam with durlobactam has shown promise, with reduced nephrotoxicity. Polymyxins, particularly colistin and polymyxin B, remain important options for treating carbapenem-resistant A. baumannii infections, with colistin being effective as a monotherapy or in combination with other agents. Tigecycline, while effective in vitro, requires higher doses for clinical success, and its use is often combined with other antibiotics. Cefiderocol has shown variable results in clinical trials, with some studies indicating its effectiveness and others showing higher mortality rates. Aminoglycosides are recommended as first-line agents for carbapenem-resistant A. baumannii infections but are typically used in combination with other antibiotics due to their limited efficacy as monotherapy. Fosfomycin and rifampicin have limited clinical effectiveness against A. baumannii and are not recommended as first-line treatments. The review emphasizes the need for continued research and the importance of using evidence-based guidelines to manage A. baumannii infections. Current recommendations suggest that sulbactam, polymyxins, tigecycline, and aminoglycosides are key options for treating MDR and XDR A. baumannii infections, with cefiderocol being a useful addition in certain cases. The guidelines from the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) support the use of these agents, highlighting the importance of tailored treatment strategies based on the patient's clinical condition and the specific resistance profile ofThe treatment of Acinetobacter baumannii (A. baumannii) infections remains a significant challenge due to its high antimicrobial resistance, particularly to beta-lactams, quinolones, aminoglycosides, and tetracyclines. A. baumannii is a major cause of nosocomial infections, especially in critically ill patients, and has been associated with severe outcomes, including high mortality rates. The bacterium's resistance profile includes resistance to carbapenems and colistin, making it difficult to treat. Recent studies highlight the importance of using effective antibiotics such as sulbactam, polymyxins (colistin and polymyxin B), tigecycline, and aminoglycosides for multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Cefiderocol has also emerged as a useful option in the treatment of these infections. Sulbactam, a beta-lactamase inhibitor, has shown clinical effectiveness against A. baumannii, particularly when used in combination with ampicillin. High-dose sulbactam (6–9 g/day) has been associated with lower mortality compared to comparator regimens. The combination of sulbactam with durlobactam has shown promise, with reduced nephrotoxicity. Polymyxins, particularly colistin and polymyxin B, remain important options for treating carbapenem-resistant A. baumannii infections, with colistin being effective as a monotherapy or in combination with other agents. Tigecycline, while effective in vitro, requires higher doses for clinical success, and its use is often combined with other antibiotics. Cefiderocol has shown variable results in clinical trials, with some studies indicating its effectiveness and others showing higher mortality rates. Aminoglycosides are recommended as first-line agents for carbapenem-resistant A. baumannii infections but are typically used in combination with other antibiotics due to their limited efficacy as monotherapy. Fosfomycin and rifampicin have limited clinical effectiveness against A. baumannii and are not recommended as first-line treatments. The review emphasizes the need for continued research and the importance of using evidence-based guidelines to manage A. baumannii infections. Current recommendations suggest that sulbactam, polymyxins, tigecycline, and aminoglycosides are key options for treating MDR and XDR A. baumannii infections, with cefiderocol being a useful addition in certain cases. The guidelines from the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) support the use of these agents, highlighting the importance of tailored treatment strategies based on the patient's clinical condition and the specific resistance profile of