For the pediatrician and neonatologist who care for term and preterm infants, the challenge remains to keep these infants free of infection after delivery in special-care nurseries and neonatal intensive care units. Studies of complications associated with term infants at risk due to maternal factors, as well as preterm infants after early delivery, have demonstrated that sepsis is a major cause of neonatal mortality and morbidity. Infections due to Gram-negative organisms are increasingly being reported from neonatal units. Moreover, Gram-negative organisms that are multidrug resistant are on the increase and pose a formidable clinical challenge. In this article, we review current epidemiology, risk factors, clinical features, diagnosis, therapy and preventive measures related to Gram-negative infections in neonates.