The use of immunosuppressive agents can be vital. However, immunosuppression may also cause reactivation of hepatitis B virus (HBV) infection which can be fatal. To reduce the risk of reactivation prophylactic antiviral treatment is recommended in patients with chronic HBV infection. In patients with former HBV infection prophylaxis is also recommended if anti-CD20 agents are used and in cases of transplantation. Immunosuppression in patients with hepatitis C virus (HCV) infection does not seem to lead to severe hepatic manifestations, and reactivation of HCV in this context generally has a mild clinical course.