Infection with hepatitis B and C virus are the two most common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. Hepatitis B virus (HBV) is a DNA virus and possesses remarkable ability to integrate in to host genome using its covalently closed circular DNA. This constitutes the major barrier in cure from HBV infection. Immune response to HBV infection is dynamic and differs with respect to age of acquisition of infection, mode of transmission of infection, and viral genotype. Nucleotide analogues are commonly used to treat HBV infection in a few selected group of patients though complete cure from the infection using these agents is unlikely. In contrast, hepatitis C virus is an RNA virus. With advent of directly acting antivirals (DAAs) management of HCV infection has been simplified and complete elimination of the virus may be achieved in near future. The aim of the chapter is to provide a brief outline of pathogenesis, clinical manifestations, and current management and prevention of HBV and HCV infection.