Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome and not an independent disease. HLH represents the extreme end of a severe uncontrolled hyperinflammatory reaction that can occur in many underlying conditions. Genetic forms of HLHs are due to defects in transport, processing and function of cytotoxic granules in natural killer cells and cytotoxic T lymphocytes, and are not restricted to manifestation in childhood. Acquired forms of HLH are encountered in infections, autoinflammatory and autoimmune diseases, malignancies, acquired immune deficiency. Functional tests allow for differentiation between genetic and acquired HLH. Treatment aims at suppressing hypercytokinemia and eliminating activated and infected cells. It includes immunomodulatory and immunosuppressive agents, cytostatics, T-cell and cytokine antibodies. In genetic HLH cure can only be achieved with hematopoietic stem cell transplantation. Reduced-intensity conditioning regimens have considerably improved survival.