Abstract Coinfection by hepatotropic viruses can occur due to the fact that hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar routes of transmission. Different clinical features of liver disease can be observed in infected patients, ranging from fulminant, acute and chronic hepatitis to hepatocellular carcinoma (HCC). The relative role of the infecting viruses in determining the final clinical picture is not yet well defined. Several reports indicate that clinical and pathological severity of liver disease among coinfected patients is increased and in patients with HCC, co-occurrence of both viruses is a common event. The potential mechanism of tumour development still remains speculative, although direct and indirect roles for both HBV and HCV have been proposed. At the molecular level, reciprocal interference of virus replication has been repeatedly described and the extent of interference is influenced by the infecting HCV genotype, genotype 1 of HCV having more efficient inhibitory activity on HBV than genotype 2. Sequence similarities between an arginine-rich nucleocapsid motif of both viruses could support these clinical observations. Concerning response rates to interferon therapy, no satisfactory results have been achieved to date, although identification of effective therapeutic schemes, based on virological status of both viruses are warranted.