Cytomegalovirus infection is one of the most common congenital infections worldwide. Moreover, it seems to be an important cause of postnatally acquired infection. Perinatal transmission can occur intrapartum (from the birth canal), from a blood transfusion, via maternal breast milk, or from close contact with infected people. The risk of breast milk-acquired cytomegalovirus infection is higher in countries with a high prevalence of cytomegalovirus immunoglobulin G-positive women. Usually, acquired cytomegalovirus infection is asymptomatic, especially in term infants. However, preterm infants can present with a sepsis-like syndrome and multiple organ involvement. A high index of suspicion is required to make an early diagnosis. Therapeutic guidelines for symptomatic postnatal cytomegalovirus infection are not yet available. More studies are required to understand the long-term sequelae of postnatally acquired cytomegalovirus infection and know which is the best strategy to avoid cytomegalovirus post-natal transmission.