In recent years, new therapeutic options have led to enormous improvements in the management of certain chronic viral infections. Nevertheless, it has also become clear that such treatments require careful consideration and follow up. At the same time, a number of new technologies have been developed to measure quantitatively the concentration of viral genome in the patient's body fluids. Initially, these tests yielded important insights into the pathogenesis of viral infections and, in the case of human immunodeficiency virus (HIV), in fact revolutionized our understanding of its natural history. In addition, however, such 'viral load' tests have become vital tools in patient management; formerly pure research tools, they are now widely used in routine virological diagnosis, and a number of commercial assays have become available. In clinical virology, viral load testing serves four purposes: for diagnosis; to assess the patient's prognosis; as therapeutic markers to monitor the effect of antiviral treatment; and to estimate the patient's infectivity, i.e. the risk of transmission. In this review paper, we summarize the current role of viral genome quantification in the clinical management of patients infected with HIV, hepatitis B virus, hepatitis C virus and those at risk of developing human cytomegalovirus-related diseases.