Congenital Cytomegalovirus (CMV) infection is one of major public health concerns and one of the most frequent congenital infections worldwide. Congenital CMV infection is under-diagnosed in the majority of asymptomatic pregnant women due to its self-limited non-specific symptoms and unimplemented screening program. Primary CMV infections are associated with the highest in-utero transmission at estimated rates of 30–35%. Transmission rate occurs less frequently in secondary CMV maternal infections at approximately 1.1–1.7%.  Congenital CMV infection can also go undetected at birth because the affected newborns are often asymptomatic, however, they manifest serious morbidities later in life. There are growing evidences that early diagnosis and treatment of newborns with congenital CMV infection can reduce sensorineural hearing loss (SNHL) and the subsequent long-term neurological and developmental disabilities. There is also increased interest in establishing a prophylactic CMV vaccine that can protect seronegative mothers from primary infection and augment the immune response in seropositive women, in order to prevent CMV reactivation or re-infection. Studies show that liquid-saliva polymerase chain reaction (PCR) assay has high sensitivity “100%" it is more advantageous than Dried blood spots (DBS) in detecting congenital CMV infection and it can be used to screen newborns in the first 3 weeks. Suggestive strategies to reduce the burden of congenital CMV disease are; establishing a screening programme for pregnant mothers, developing prophylactic CMV vaccine, early therapeutic intervention in pregnant women and newborns and use Saliva PCR assay as a new method for neonatal CMV screening.