| Hemophagocytic syndrome (HPS) is a rare but distinct condition caused by inappropriate and dysregulated activation of the immune system. HPS is characterized by febrile hepatosplenomegaly, pancytopenia, hypofibrinemia and liver dysfunction; these changes are associated with the infiltration of bone marrow and organs by nonmalignant macrophages that phagocytose blood cells. Primary HPS is linked to inherited immune dysregulation, whereas secondary HPS tends to be triggered by an infectious or neoplastic disease. Multiorgan failure can complicate this life-threatening condition and renal involvement has frequently been reported; however, precise descriptions of the renal manifestations of HPS are lacking. Acute kidney injury due to tubular necrosis is the most common renal presentation, but nephrotic syndrome can also occur. HPS can be observed in immunocompromised patients and nephrologists must be aware that this condition can occur in renal transplant recipients. Mortality in patients with HPS can be as high as 50%. Despite considerable advances in the treatment of familial HPS, no specific therapy has demonstrated a consistent capacity to control reactive HPS when combined with suppression of the triggering factor. This Review summarizes the presentation, causes, pathophysiology and renal features of HPS for the benefit of the practicing nephrologist.