HLH remains a challenging disease to diagnose and treat. New data on biologic markers helps to clarify the diagnostic criteria. The genetics of inflammatory respnse in pediatric sepsis will be discussed as a correlary to the hyperactive immune response to HLH. The role of reduced intensity conditioning for stem cell transplants will be reviewed In 2009 the LCH-IV treatment protocol will be opened. It is critical that more physicians are aware of this and register patients on study. We will describe the protocol and innovations to facilitate registration and data entry. Central Nervous System LCH is confusing and treatments poorly undestood. This conference will clarify issues surrounding the risk factors, diagnosis and treatment of CNS-LCH. The onging debate regarding Langerhans Cell Histiocytosis pathobiology: Cancer or immune dysregulation? We will review recent studies in LCH lesion immunology and dendritic cell biology that add even more complexity to LCH discussions