Liver disease caused by hepatotrophic viruses imposes a substantial burden on health care resources. Persistent infections from hepatitis B virus (HBV), hepatitis C virus, and hepatitis delta virus result in chronic liver disease, while hepatitis A virus and hepatitis E virus produce a self-limited disease. Effective hepatitis B vaccines that provide long-term protection against chronic HBV infection have been available for > 10 years, while inactivated hepatitis A vaccines have recently been shown to prevent acute disease. To prevent transmission of HBV, scientifically and epidemiologically sound recommendations call for vaccination of all infants in successive birth cohorts worldwide. For hepatitis A vaccines, recommendations will be developed in the near future and should reflect vaccine performance and the epidemiology of hepatitis A. A number of policy, health care financing, and educational issues must be addressed to ensure the effective use of both of these vaccines.