Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenias, splenomegaly, and hemophagocytosis by macrophages activated by high cytokine levels. Chronic granulomatous disease (CGD) is characterized by recurrent infections, hyperinflammation, and excessive cytokine release. This may predispose patients with CGD to developing HLH during an infection. We conducted a retrospective review of patients with CGD, treated at our institution between 1999 and 2008. Three out of 17 patients developed HLH. Patients with CGD may be at increased risk for developing HLH. Remission of HLH was achieved after treatment with antimicrobials, steroids, and intravenous immunoglobulin This approach to treatment appears to be effective. Pediatr Blood Cancer 2011;56:460–462. © 2010 Wiley-Liss, Inc.