Nosocomial infections or hospital-acquired infections continue to be a serious threat to all patients, particularly newborns, who have immature immune systems. Critically ill neonates have increased risk for nosocomial infections due to longer hospital stays, use of diagnostic and therapeutic devices, and more frequent exposure to hospital treatment staff. This paper reviews several microorganisms known to cause nosocomial infection (group B streptococci, methicillin-resistant staphylococci, human immunodeficiency viruses, and rotaviruses), as well as problems associated with early detection and important practices for achieving optimal control and prevention.