Postnatal cytomegalovirus (pCMV) infection is a common viral infection typically occurring within the first months of life. pCMV refers to postnatal acquisition of CMV rather than postnatal manifestations of antenatal or perinatal acquired CMV. pCMV is usually asymptomatic in term infants, but can cause symptomatic disease in preterm (gestational age <32 weeks) and very low birth weight (<1500 g) infants resulting in sepsis, pneumonia, thrombocytopaenia, neutropaenia, hepatitis, colitis and occasionally death. There are significant uncertainties regarding the management of premature infants with pCMV disease which is in part due to our limited understanding of the natural history of this disease. This review describes the current epidemiology and clinical manifestations of pCMV disease which should alert clinicians to test for CMV and also outlines a strategy to manage the condition.