Kawasaki disease (KD) is an acute, self-limiting, small-vessel vasculitis with an unknown cause that affects children between the ages of 6 months and 5 years. It is the most common cause of acquired coronary artery disease in childhood. Acute myocardial infarction and coronary artery aneurysm are major complications. Although an infectious agent is highly suspected, the etiology of KD is unknown. Significant progress has been, however, toward understanding the natural history of this disease, and therapeutic interventions have been developed that halt the immune-mediated destruction of the vascular system. The pathology of the necrotizing vaculitis of KD suggests a primary role for monocytes-macrophages and T lymphocytes in the acute vascular injury observed. KD fits nicely in the spectrum between an infectious disease and a true autoimmune disease, with an infectious trigger leading to a prolonged self-directed immune response. This review focuses on recent data concerning the immunopathogenesis of vascular damage, and the involvement of CD4+CD25+ regulatory T cells (Treg) in KD.