Resistance to antimicrobial agents, which was recognized more than 50 years, continues to be a major cause of increased morbidity, mortality and health care cost. Overuse of antibiotics is considered the major contributing factor; however, poor implementation of infection control measures, prolonged hospitalization, admission to intensive care units and the use of invasive procedures are other contributing factors. The authors review the epidemiology, mechanism of resistance, treatment options and prevention measures of infections caused multi-drug resistant S. pneumoniae, methicillin-resistant S. aureus (MRSA), macrolide-resistant S. pyogenes and vancomycin-resistant enterococci (VRE) in pediatric patients. Antibacterial resistance among Gram-negative organisms, including extended spectrum beta-lactamase (ESBL) producing enteric bacteria, and the management and prevention of infections caused by these organisms are also discussed.