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The World Health Organization estimates an annual total of 1.5 million clinical cases of hepatitis A worldwide, but seroprevalence data indicate that tens of millions of hepatitis A virus infections occur each year. In the United States in the 1980s–1990s, an average of 26,000 acute hepatitis A cases were reported per year, representing approximately 270,000 infections annually. Since licensure of effective hepatitis A vaccines in the mid-1990s, US hepatitis A rates have fallen precipitously—particularly since 1999, when routine childhood vaccination was recommended in states with consistently elevated rates. By 2004, the overall rate had declined to 1.9/100,000 population, the lowest rate ever recorded and 79% lower than any previously recorded nadir. These marked declines occurred with relatively modest vaccination coverage, suggesting that strong herd immunity accompanies the initiation of routine vaccination programs. Routine childhood vaccination has produced similar results in Israel and selected regions of Italy, Spain, and Australia. Hepatitis A vaccination will probably remain a low priority for some time in the poorest countries, where most persons are infected as young children. However, shifts in the epidemiologic patterns of disease associated with declining hepatitis A virus transmission are occurring in many regions of the world. These shifts are likely to create circumstances where strategically targeted vaccination of children could produce substantial public health benefits.