Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach ≥5 positive criteria out of the 8 HLH-2004 criteria can be time consuming and may delay timely initiation of treatment. Moreover, it is still uncertain which of these criteria should be monitored to predict remission of HLH. Finally, new therapeutic options, targeting immunopathways associated with immune dysregulation have recently become available. In this project we have acquired a retrospective cohort that consists of 87 HLH patients that were treated between 2006 and 2016 in five Dutch tertiary centers. We have collected data regarding HLH diagnosis, treatment and follow-up and are using data driven statistical methods to identify diagnostic and prognostic variables specific for HLH and promising therapeutic regimens. With this approach we aim to improve HLH diagnosis, prognosis and treatment in the future.