The issue of antibiotic resistance has been around ever since the first antibiotic penicillin was introduced to the world. It continues to rise, becoming a major problem across the globe and Malaysia is no exception. Hospital is a critical component of the antibiotic resistance problem worldwide. The problems of antibiotic resistance are typically magnified in a hospital setting due to the common variables in the hospital environment that favour its development. These include a combination of highly susceptible patients, intensive and prolonged antibiotic use, and crossinfection resulting in nosocomial infections with highly resistant bacterial pathogens such as multi-resistant gram-negative rods, vancomycin resistant enterococci (VRE) and methicillinresistant Staphylococcus aureus (MRSA) as well as resistant fungal infections. Transmission of highly resistant bacteria from patient to patient within the hospital environment amplifies the problem of antibiotic resistance and may result in the infection of patients who are not receiving antibiotics. Transmission of antibiotic-resistant strains from hospital personnel to patients or vice versa may also occur. What are the available strategies and what works best in managing antibiotic resistance in the hospital? This review will highlight the seriousness of the resistance problem and identify actions that address it especially in the context of improving the problem in Malaysian hospitals.