Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is a rare and potentially fatal complication of Kawasaki disease (KD). We report 2 cases, performed a literature search, and analyze the characteristics of MAS associated with KD. A total of 69 patients were evaluated, 34 reported the date of the diagnosis of MAS and KD, 6% had a diagnosis of MAS before KD, 21% had a simultaneous presentation, and 73% had the diagnosis of MAS after KD. Different treatment approaches were observed with corticosteroids administered in 87%, cyclosporine in 49%, etoposide (VP-16) in 39%, and monoclonal anti-TNF in 6% of cases. Coronary abnormalities were especially high in this group of patients (46%) and 9 patients died (13%). The persistence of fever with splenomegaly, hyperferritinemia, thrombocytopenia, and elevated aspartate aminotransferase (AST) should prompt the consideration of MAS complicating KD.