Neonatal infections range from early-onset vertically acquired infections to nosocomial bacterial sepsis, and they account for significant morbidity and mortality globally. The recent emergence of perinatally acquired HIV-1 infection has also placed an enormous burden on existing meager health resources in developing countries. The risk of early-onset group B streptococci sepsis may be related to heavy genital tract colonization at term. Perinatally acquired HIV-1 infection also occurs at birth, with higher rates of infection after vaginal delivery. Detection of circulation HIV-1 viral DNA by polymerase chain reaction offers an extremely sensitive screening method in the neonatal period. In contrast, rapid confirmation of bacterial sepsis in the newborn still poses considerable problems. A review of data on antimicrobial prophylaxis of preterm premature rupture of membranes does reveal improved neonatal outcome. However, the rapid and widespread emergence of multidrug resistance among bacterial pathogens dictates the need for judicious use of antibiotics, as well as close attention to preventive strategies.