Kawasaki syndrome (KS) is the most common cause of acquired pediatric heart disease in the developed world. There have been 2 distinctive patterns for the emergence of KS that are likely related to several factors including exposure to the causative agent (s) and host genetics. In Europe and North America where we presume the genetic susceptibility seems to be low, KS has existed in the pediatric population for more than a century and is associated with relatively low incidence. In Japan where genetic susceptibility is presumed to be high, KS seems not to have existed before the early 1950s. This relatively recent exposure has resulted in 3 nationwide epidemics and a high current endemic rate of 200 per 100,000 in children less than 5 years. If our history of alternative patterns of the emergence of KS is valid, it may prove useful as a predictive tool for countries including India, where clusters of KS cases have been recently reported. This article examines the historical evidence in support of a 2-tiered emergence of KS in Euro-America and Japan and then returns briefly to discuss its implications for the pediatric populations of India and the health care delivery systems in the developing world.