The incidence of transfusion-associated hepatitis in the United States has fallen dramatically since the late 1960s. Where once the risks were so great that as many as one in three transfused patients contracted hepatitis, now they are infinitesimal. Many factors share responsibility for this accomplishment; however, two stand above the rest: (i) improved donor selection and screening criteria, especially elimination of paid blood donations; and (ii) major advances in testing for viral hepatitis carriers. Currently, four tests are used for the prevention of transfusion-associated hepatitis: (i) hepatitis B surface antigen; (ii) hepatitis C virus antibody; (iii) hepatitis B core antibody; and (iv) alanine aminotransferase. The first two tests are largely responsible for the current low risks of transfusion-associated hepatitis due to hepatitis B virus and hepatitis C virus of 1 in 63 000 and 1 in 125 000, per unit, respectively. To further reduce the risks of transfusion-associated hepatitis will require the enhanced sensitivity provided by nucleic acid amplification techniques (e.g. polymerase chain reaction). Currently, however, no such tests are licensed and practical, automated, or inexpensive enough for individual blood donor screening. We have made such great strides in the prevention of transfusion-transmitted hepatitis that background rates of viral hepatitis now greatly exceed the risk of transmission via transfusion. For this reason, while it may still be reasonable to consider a transfusion as a possible cause for hepatitis, it is imperative that many other possibilities (e.g., iatrogenic and other risk factors) be ruled out.