Hemophagocytic lymphohistiocytosis (HLH) is a multisystem inflammatory disorder due to cytokine overproduction from excessively activated lymphocytes and macrophages. HLH has been divided into two subgroups: primary HLH and secondary HLH. Primary HLH includes PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A and XIAP gene mutations; and secondary HLH is associated with infections, malignancies and autoimmune diseases. Among primary HLH-related genes, SH2D1A and XIAP are genetically responsible for X-linked lymphoproliferative syndrome (XLP) due to signaling-lymphocytic-activation-molecule-associated protein (SAP) and XIAP deficiencies, respectively. XLP is characterized by extreme vulnerability to Epstein–Barr virus infection. The major clinical manifestations of XLP consist of HLH (60%), lymphoproliferative disorder (30%) and dysgammaglobulinemia (30%). Analysis of clinical phenotypes of XLP patients suggests that XLP predominantly shows familial HLH phenotypes, whereas some XLP patients present sporadic HLH. For many decades, clinicians and investigators have been concerned with possible XLP in young boys presenting with Epstein–Barr-virus-associated HLH. This review aims to describe the new knowledge about XLP and to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH.