Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of extreme inflammation occurring in association with genetic defects involving the granule-dependent cytotoxic pathway of CD8+ T cells or NK cells and/or a wide variety of triggers including infections, malignancies, and rheumatologic disorders. Because of its relative rarity and the non-specific nature of the individual clinical and laboratory abnormalities comprising the characteristic “pattern” of HLH, the diagnosis can be elusive. Furthermore, some of the laboratory tests included in the diagnostic criteria are time-consuming or not widely available, and since many of these patients are critically ill, HLH must be considered early on so that the diagnosis can be established and potentially life-saving treatment initiated. Since the diagnosis of HLH is truly a clinicopathologic correlation, in this article, we as a team of pediatric clinical and laboratory physicians will use exemplary cases from our own institution with a variety of clinical presentations to illustrate the many “faces” of HLH; deconstruct the diagnosis; point out some of the challenges, limitations, pearls and pitfalls; and make it easier to understand the pathophysiology in context. However, while we may see relatively more cases working in a tertiary care children’s hospital, HLH is a disease of both children and adults.