Chronic liver disease (CLD) is highly prevalent, and hepatitis C is one of the leading causes. Acute hepatitis A or B in patients with chronic hepatitis C can lead to more severe hepatic injury and a higher fatality rate than in patients without hepatitis C. Thus, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention and the World Health Organization recommend that persons with CLD be vaccinated against hepatitis A virus (HAV), and the ACIP and the National Institutes of Health recommend vaccination against both HAV and hepatitis B virus (HBV) in patients with chronic hepatitis C. Because coinfection with HAV or HBV in patients with chronic hepatitis C or CLD is common, antibody screening prior to hepatitis A or B vaccination can identify patients who are already immune to these viruses and thus do not need to be vaccinated. Selective hepatitis A vaccination (i.e., vaccination of patients who test negative for either HAV antibody immunoglobulin G or total antibodies to HAV) is most cost-effective in areas where the local prevalence of hepatitis A is higher than the national prevalence and in populations with higher background rates of HAV exposure compared with the general population, such as older adults, foreign-born patients, African Americans, and persons with CLD or hepatitis C. Although not usually recommended for healthy adults or those with compensated CLD because of virtually 100% postvaccination seroconversion, serologic testing after hepatitis A vaccination is recommended in patients with decompensated or advanced end-stage liver disease because of the much lower seroconversion rates in these patients. Selective vaccination against HBV in patients with CLD or hepatitis C is also recommended. Testing for hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) is considered the most efficient and reasonably cost-effective method to screen for hepatitis B serologic markers because HBsAg identifies individuals with both acute and chronic HBV infection, and anti-HBs identify those who are immune secondary to vaccination or past infection. Testing for antibodies to hepatitis B core antigen is needed to further distinguish between immunity due to vaccination and immunity due to past infection, but it is not recommended as the only screening test for HBV immunity. Postvaccination testing for hepatitis B seroconversion is recommended in all patients with CLD, especially in those with more advanced disease, because the rate of seroconversion is generally lower than in healthy adults. If patients with CLD are not adequately protected after a standard course of hepatitis B vaccination, a repeat course of vaccination using the standard schedule or an accelerated schedule (days 0, 7, and 21) should be considered.