Human cytomegalovirus (CMV) infection is a very common lifelong infection in South Africa, with intermittent periods of silent reactivation. Infection is spread by intimate contact with infected body fluids (urine, saliva, milk, semen and blood) and most commonly takes place silently in childhood. Clinical disease is rare but may be associated with one or more of the following: (i) a large dose of virus; (ii) a primary infection; and (iii) infection at a time of poor or impaired cellular immunity (developing fetus, after organ transplantation). CMV is an important but rare cause of congenital disease involving especially hearing and neurological deficits. It is often found after organ transplantation but its precise role is not clear. Interpretation of cytomegalovirus tests in connection with an undiagnosed illness is rendered very difficult by the ubiquitous, silently reactivating nature of the virus in both health and disease. An aetiological role is easily assumed but not easily proved.