HIV co-infection influences the course and natural history of hepatitis B virus (HBV) infection by impairing the quantity and quality of the innate and adaptive immune response. The rates of spontaneous resolution after acute infection and spontaneous anti-HBe and anti-HBs seroconversions are decreased, and levels of HBV replication are increased in HIV-infected patients. A more rapid progression of liver fibrosis and a higher rate of cirrhosis decompensation (but not hepatocellular carcinoma) have been demonstrated in co-infected patients. The risk of HBV-associated end-stage liver disease and liver-related mortality may be increased by HIV co-infection. Antiretroviral therapy may trigger spontaneous anti-HBe and anti-HBs seroconversion and/or a better immune control of HBV replication by restoring adaptive immunity, but can also increase hepatitis flares. Reactivation of chronic hepatitis B has been observed after suspension of anti-retrovirals with anti-HBV activity or after occurrence of HBV resistance to lamivudine. Future research should focus on: the impact of HIV-induced changes in innate and adaptive immune response and modifications induced by anti-retroviral therapy that may impact on progression of advanced chronic hepatitis B; the association between HBV genotype and clinical course of disease; and the role of occult HBV infection as a co-factor with other causes of liver injury.