Kawasaki Disease (KD) is a systemic vasculitis affecting young children, often leading to coronary artery aneurysms. The exact etiology remains unknown, but recent epidemiological data from Japan, the country with the highest incidence, provide new clues. The disease emerged in Japan after World War II and has since seen three nationwide epidemics in 1979, 1982, and 1986, suggesting the introduction of a novel agent. The subsequent stable plateau of cases and the annual rise in school-age children indicate increasing exposure to an environmental trigger, possibly wind-borne aerosols. The COVID-19 pandemic reduced KD cases globally, likely due to social distancing measures, highlighting the role of person-to-person transmission. However, the pandemic did not explain the overall increase in KD cases in Japan. Other hypotheses include environmental factors such as air pollution and oxidative stress, as well as genetic variations. Research efforts are ongoing to identify specific diagnostic tests and targeted therapies, with a focus on understanding the etiology, which could lead to more effective treatments and better management of KD.Kawasaki Disease (KD) is a systemic vasculitis affecting young children, often leading to coronary artery aneurysms. The exact etiology remains unknown, but recent epidemiological data from Japan, the country with the highest incidence, provide new clues. The disease emerged in Japan after World War II and has since seen three nationwide epidemics in 1979, 1982, and 1986, suggesting the introduction of a novel agent. The subsequent stable plateau of cases and the annual rise in school-age children indicate increasing exposure to an environmental trigger, possibly wind-borne aerosols. The COVID-19 pandemic reduced KD cases globally, likely due to social distancing measures, highlighting the role of person-to-person transmission. However, the pandemic did not explain the overall increase in KD cases in Japan. Other hypotheses include environmental factors such as air pollution and oxidative stress, as well as genetic variations. Research efforts are ongoing to identify specific diagnostic tests and targeted therapies, with a focus on understanding the etiology, which could lead to more effective treatments and better management of KD.