Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, primarily associated with respiratory infections in humans. It has been identified as a significant nosocomial pathogen, causing a range of infections, including pneumonia, bacteremia, biliary sepsis, and urinary tract infections. The bacterium is highly adaptable and can survive in various environments, including water systems, soil, and medical devices. Its ability to form biofilms and resist multiple antibiotics makes it a challenging infection to manage. The article reviews the historical and clinical significance of S. maltophilia, highlighting its increasing incidence in hospital settings, particularly among immunocompromised patients. It discusses the bacterium's resistance to various antibiotics, including β-lactams, macrolides, and fluoroquinolones, and the emergence of multidrug resistance (MDR) strains. The text also explores new treatment strategies, such as combination therapies and the use of cationic peptides and nanoemulsions, which show promise in overcoming antibiotic resistance. The article emphasizes the need for continued surveillance and monitoring of S. maltophilia to combat its spread and improve patient outcomes. It concludes by discussing the potential of alternative treatments, such as plant essential oils, which have shown antibacterial activity against S. maltophilia.Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, primarily associated with respiratory infections in humans. It has been identified as a significant nosocomial pathogen, causing a range of infections, including pneumonia, bacteremia, biliary sepsis, and urinary tract infections. The bacterium is highly adaptable and can survive in various environments, including water systems, soil, and medical devices. Its ability to form biofilms and resist multiple antibiotics makes it a challenging infection to manage. The article reviews the historical and clinical significance of S. maltophilia, highlighting its increasing incidence in hospital settings, particularly among immunocompromised patients. It discusses the bacterium's resistance to various antibiotics, including β-lactams, macrolides, and fluoroquinolones, and the emergence of multidrug resistance (MDR) strains. The text also explores new treatment strategies, such as combination therapies and the use of cationic peptides and nanoemulsions, which show promise in overcoming antibiotic resistance. The article emphasizes the need for continued surveillance and monitoring of S. maltophilia to combat its spread and improve patient outcomes. It concludes by discussing the potential of alternative treatments, such as plant essential oils, which have shown antibacterial activity against S. maltophilia.