The article discusses the global health crisis posed by antimicrobial resistance, particularly in Gram-negative bacteria, and the urgent need for new antibiotics. The World Health Organization (WHO) has categorized these bacteria into critical, high, and medium priority groups based on the severity of their resistance and the need for new antibiotics. Gram-negative bacteria are more resistant than Gram-positive bacteria due to their unique cell structure, which includes an outer membrane that protects them from antibiotics. The article outlines several strategies to combat resistant Gram-negative bacteria, including the development of antimicrobial adjuvants, structural modifications of existing antibiotics, and the exploration of novel chemical structures with new mechanisms of action. Key resistant Gram-negative bacteria discussed include *Enterobacteriaceae*, *Acinetobacter baumannii*, *Pseudomonas aeruginosa*, *Helicobacter pylori*, *Campylobacter*, *Salmonella spp.*, *Neisseria gonorrhoeae*, and *Shigella spp.* Each of these bacteria has developed resistance mechanisms such as β-lactamases, efflux pumps, and target site modifications. The article also reviews recent advancements in treatment approaches, including the use of antibiotic adjuvants like β-lactamase inhibitors, and alternative therapies such as bacteriophages, DCAP, Odilorhabdins (ODLs), peptidic benzimidazoles, and quorum sensing (QS) inhibitors. The article emphasizes the importance of continued research and development to discover new antibiotics and alternative therapies to combat the growing threat of antimicrobial resistance.The article discusses the global health crisis posed by antimicrobial resistance, particularly in Gram-negative bacteria, and the urgent need for new antibiotics. The World Health Organization (WHO) has categorized these bacteria into critical, high, and medium priority groups based on the severity of their resistance and the need for new antibiotics. Gram-negative bacteria are more resistant than Gram-positive bacteria due to their unique cell structure, which includes an outer membrane that protects them from antibiotics. The article outlines several strategies to combat resistant Gram-negative bacteria, including the development of antimicrobial adjuvants, structural modifications of existing antibiotics, and the exploration of novel chemical structures with new mechanisms of action. Key resistant Gram-negative bacteria discussed include *Enterobacteriaceae*, *Acinetobacter baumannii*, *Pseudomonas aeruginosa*, *Helicobacter pylori*, *Campylobacter*, *Salmonella spp.*, *Neisseria gonorrhoeae*, and *Shigella spp.* Each of these bacteria has developed resistance mechanisms such as β-lactamases, efflux pumps, and target site modifications. The article also reviews recent advancements in treatment approaches, including the use of antibiotic adjuvants like β-lactamase inhibitors, and alternative therapies such as bacteriophages, DCAP, Odilorhabdins (ODLs), peptidic benzimidazoles, and quorum sensing (QS) inhibitors. The article emphasizes the importance of continued research and development to discover new antibiotics and alternative therapies to combat the growing threat of antimicrobial resistance.