Accurate diagnosis of viral hepatitis is based on determination of specific viral markers. In HBV infection they include HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, IgM anti-HBc, and HBV DNA. There are patients with HBV marker constellation indicating serologic recovery, but with HBV DNA in the liver indicating continuous viral replication. Mutations have been described in all four HBV genes. It is important to take into account the main precore mutation which leads to a decrease or complete inhibition of HBeAg production (HBeAg negative HBV infection). Diagnostically most important are surface gene mutations because they can result in the false diagnosis or delay in diagnosis in important groups of patients. Anti-HCV and HCV RNA are found in sera of patients with HCV infection. A false positive result is possible with ELISA, especially in patients with low c/o ratio and in all individuals with a low risk of HCV infection. It is necessary to confirm ELISA positivity with confirmation techniques (western blot, immunoblot). There are qualitative and quantitative assays for HCV RNA determination. HCV genotyping should be done, since different viral genotypes respond differently to therapy and therapeutic protocols are different. It is possible to determine HCVAg free or complexed with the antibody. Determination of free HCVAg could enable the diagnosis of acute HCV infection. There are some clinical situations where the interpretation of HBV and HCV markers is difficult because of ambiguous interpretation and "unusual" constellation. Attention should be focused on simultaneous infection within other hepatitis viruses or other viruses like HIV. Replication of one virus could have a direct influence on the replication and expression of another virus.