Macrophage activation syndrome (MAS) is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of T lymphocytes and macrophages. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically similar to MAS, highlight the possible pathogenetic role of a defective function of perforin, a protein involved in the cytolytic processes and control of lymphocyte proliferation. The clinical features of MAS include fever, liver derangement, renal involvement in form of proteinuria or high creatinine, CNS involvement in form of convulsions, psychiatric disturbances, hepatosplenomegaly and lymphadenopathy. Early diagnosis can be difficult. Measurement of the serum ferritin level may assist in the diagnosis and may be a useful indicator of disease activity, therapy response, and prognosis. The recognition that MAS belongs to the secondary or reactive hemophagocytic syndromes has led to the proposal to rename it according to the contemporary classification of histiocytic disorders. Bone marrow may show hemophagocytosis. Cyclosporin A has been found effective in patients with corticosteroid-resistant MAS.