HBV and HCV are both hepatotrophic pathogens that share common routes of transmission, namely through exposure to infected blood and body fluids. Available natural history studies suggest dual infection with HBV and HCV increases the risk of progressive liver disease, and the risk of cirrhosis and liver cancer. Owing to the dynamic nature of these chronic infections, with fluctuations in viral level and disease activity, close monitoring is needed to determine the appropriate time to intervene with treatment. The clinical profile most commonly encountered is for active HCV infection (HCV RNA-positive) with or without active HBV infection (HBsAg-positive with variable HBV DNA levels). For these patients, treatment with pegylated interferon and ribavirin is the treatment of choice. For those with HBV-predominant disease (and HCV RNA-undetectable), the treatment is identical to that with HBV infection alone. For patients unresponsive to these initial treatments, there are no specific guidelines, and additional studies to define the treatment algorithms for nonresponders or relapsers are needed.