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Human cytomegalovirus (CMV) is a well-known cause of morbidity and mortality in transplantation patients. Monitoring of CMV reactivation from latency is critical for these patients. The key to efficient and effective management of CMV infection is a test capable of rapidly monitoring and quantifying the presence of CMV in the blood. This is essential for the identification of subjects at high risk of developing CMV disease, for example, patients receiving steroid or immunosuppressive compounds for accelerated graft-versus-host disease, transplant rejection and also for the application and monitoring of pre-emptive antiviral therapeutic strategies. The assays presently available and frequently used in this setting include conventional and shell vial culture, the CMV antigenemia assay, PCR for CMV DNA, hybrid capture assay for CMV DNA and detection of CMV RNA by nucleic acid sequence-based amplification. The low sensitivity and low reproducibility of conventional cell culture and shell vial assays limit their role in the management of CMV infection to one of disease diagnosis. Diagnostic assays, such as the pp65 antigenemia and other molecular assays, have improved the ability to diagnose CMV disease quickly and accurately. These methods fulfill the requirements for a good diagnostic assay: they have high sensitivity, most can quantify viral load and they are rapid and reproducible. Their characteristics allow these assays to be used to predict the development of CMV disease and monitor response to therapy.