Cytomegalovirus (CMV) is the leading cause of congenital infection in humans and constitutes a major public health problem. Congenitally infected infants, both symptomatic and asymptomatic at birth, are at risk for sequelae including sensorineural hearing loss. The virus can be transmitted to the fetus following either a primary or a non-primary maternal infection during pregnancy. Even though the transmission rate is much higher in primary infected mothers than in mothers with preconceptional immunity, routine CMV screening of pregnant women is not recommended today because no consensus exists on prenatal treatment options. Intravenous ganciclovir or oral valganciclovir are used to treat neonates with symptoms at birth. Valganciclovir treatment for 6 months is recommended for congenitally infected neonates with moderately to severely symptomatic disease. All infants with congenital CMV infection, both symptomatic and asymptomatic at birth, need a follow-up evaluation to detect sequelae promptly. For several years, a universal screening for congenital CMV infection has been suggested by many authors for early detection of sequelae and timely intervention. A real-time PCR assay of saliva specimens seems to offer the best characteristics for use in screening.