Purpose of reviewHemophagocytic lymphohistiocytosis (HLH) is a condition of uncontrolled immune activation with a high mortality rate. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH. However, HLH is still a refractory disease for which the search for novel treatments continues. This article overviewed recent advances in treatment of HLH.Recent findingsCurrent practices in treatment extend from chemo-immunotherapy to some new cytokine-targeting biologicals, which are more effective to eliminate pathologically activated T cells and resist exaggerated cytokine storm. Preliminary results showed that some novel approaches to refractory HLH would potentially improve outcome of the fatal disease. Allogeneic hematopoietic stem cell transplantation after HLH remission represents the final solution for replacing defective cytotoxic T cells and even treating some underlying disease processes to prevent disease recurrence.SummaryA uniform protocol and algorithm for the treatment would not be appropriate for each patient given the heterogeneity of the underlying conditions. Further improvements in therapy require prospective trials to develop reasonable strategies for HLH patients in different subtypes, based on the underlying trigger, disease severity, as well as genetic background.