Its high diagnostic accuracy, rapidity, quantitative nature and technical simplicity have made the cytomegalovirus (CMV) antigenaemia assay one of the cornerstone methods for diagnosis and management of active CMV infection in immunocompromised patients. Many technical variations have been introduced in an effort to optimize the assay. Now, standardization of the assay and quality control are becoming of increasing importance. In this review we first discuss the nature and origin of the CMV antigens in distinct blood cells during active CMV infection. Further, some of the most important technical variations of the assay are considered and a proposal for standardization is made to indicate how quality control might be achieved. Acceptance of these proposals by the international community would be an important step forward, e.g. towards multicentre antigenaemia-directed intervention studies.