Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by immune dysregulation and hyperinflammation and is histologically characterized by the presence of benign hemophagocytic macrophages. HLH is classified as primary or secondary depending on the underlying etiology and includes conditions with various pathophysiological features. The pathogenic mechanisms underlying the different HLH subtypes remain incompletely understood and therapeutic regimens for HLH are devised on empirical bases. Herein, recent advances in the understanding of HLH pathogenesis and potential strategies for subtype-specific HLH treatment are reviewed.