Since the discovery of hepatitis C virus, the availability of serological hepatitis C virus screening has led to the identification of many subjects with normal aminotransferase levels who are chronically infected by the hepatitis C virus. To date, the epidemiology and natural history of subjects with normal aminotransferase levels are far from being clarified. Further, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial, and benefit from interferon treatment in this group of patients is yet to be proven. On account of the consistent normality of aminotransferases, it is not easy to calculate the rate of persons with normal aminotransferase levels among chronic hepatitis C virus carriers, nor their prevalence in the general population. It has been estimated that up to 25% of patients with chronic hepatitis C virus infection have persistently normal aminotransferase levels (10% to 40%, according to different studies). Most studies showed a clear prevalence of females, ranging from 58% to 90%. Liver biopsy shows some degree of chronic liver disease in up to 80% of these subjects, although in the majority, histological damage is mild and probably does not progress to more severe liver disease, moreover, the progression to fibrosis is slower than in patients with elevated aminotransferase levels. Virological features of these subjects (hepatitis C virus genotype distribution, viral load, quasispecies diversity) do not differ with respect to patients with elevated aminotransferase levels although a higher frequency of non 1 hepatitis C virus types has been reported. To date, no biochemical or virological tools to assess the presence and severity of liver damage exist. Antiviral treatment with interferon may induce a long-term response in only a small proportion of hepatitis C virus carriers with persistently normal aminotransferase levels, and many patients develop aminotransferase-flare-up during or shortly after treatment. Thus, interferon or combination antiviral treatment of hepatitis C virus carriers with normal aminotransferase values should be avoided in clinical practice.