Antimicrobial resistance constitutes a public health menace globally, affecting treatment outcomes in healthcare settings. This problem is exacerbated in Gram-negative bacteria including Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, E. coli, Salmonella spp., and others belonging to the Enterobacteriaceae family. These organisms have developed resistance mechanisms that render common antibiotics ineffective, making infections caused by these pathogens difficult to treat. Particularly, unregulated antibiotic use, selective pressure, and horizontal gene transfer are some of the contributors to their resistance to the available antibiotics. Effective antimicrobial stewardship plays a crucial role in managing these infections and preventing their further escalation through Antimicrobial Stewardship programs, de-escalation therapy, combination therapy, antibiotics dose optimization, and prophylactic antibiotic are used in those at high risk of infection. Education and training are vital for healthcare providers to enhance their knowledge of antimicrobial stewardship principles and implementation.