Antimicrobial resistance is a major global health threat, with many bacteria now resistant to all antibiotics. The World Health Organization (WHO) has identified priority pathogens that require new antibiotics, categorized as critical, high, or medium priority. Gram-negative bacteria are particularly resistant due to their complex cell wall structure, which includes an outer membrane that prevents many antibiotics from entering the cell. Strategies to combat resistance include developing new antibiotics, modifying existing ones, and exploring novel mechanisms of action. Research has focused on β-lactamase inhibitors, which block resistance mechanisms, and natural products like bacteriophages, DCAP, Odilorhabdins, peptidic benzimidazoles, and quorum sensing inhibitors. These agents target different aspects of bacterial survival, such as cell wall synthesis, membrane integrity, and biofilm formation. Despite progress, antibiotic resistance remains a critical challenge, prompting the search for alternative therapies. New approaches, including phage therapy and synthetic compounds, are being explored to address the growing threat of resistant bacteria.Antimicrobial resistance is a major global health threat, with many bacteria now resistant to all antibiotics. The World Health Organization (WHO) has identified priority pathogens that require new antibiotics, categorized as critical, high, or medium priority. Gram-negative bacteria are particularly resistant due to their complex cell wall structure, which includes an outer membrane that prevents many antibiotics from entering the cell. Strategies to combat resistance include developing new antibiotics, modifying existing ones, and exploring novel mechanisms of action. Research has focused on β-lactamase inhibitors, which block resistance mechanisms, and natural products like bacteriophages, DCAP, Odilorhabdins, peptidic benzimidazoles, and quorum sensing inhibitors. These agents target different aspects of bacterial survival, such as cell wall synthesis, membrane integrity, and biofilm formation. Despite progress, antibiotic resistance remains a critical challenge, prompting the search for alternative therapies. New approaches, including phage therapy and synthetic compounds, are being explored to address the growing threat of resistant bacteria.