Hemophagocytic Lymphohistiocytosis (HLH), which is a severe, potentially fatal condition characterized by T lymphocyte overactivation, is predominantly caused by infections, hematological malignancies, and autoimmune conditions. HLH due to therapy with Immune Checkpoint Inhibitors (ICI) has rarely been reported. We describe a 60-year-old male with metastatic melanoma who developed HLH after the initiation of nivolumab plus ipilimumab treatment. Prompt diagnosis and high-dose mono-prednisolone therapy resulted in rapid resolution of his subjective symptoms and laboratory findings. Apart from this case presentation we provide a brief overview on clinical characteristics of previously observed ICI-induced HLH cases. Given the increasing use of ICI in a variety of cancers, the frequency of HLH will very likely raise. HLH morbidity and mortality are often the result of delayed diagnosis and inappropriate treatment. Hence, HLH must be considered in ICI-treated cancer patients who present with symptoms such as fever, cytopenias and hyperferritinemia.