Background: Cancer can escape the immune system through different mechanisms. One of which is the expression of program death ligand-1 (PD-L1). This ligand binds to PD-1 receptor on activated T cells, subsequently leading to inhibition of the immune response. Nivolumab is novel antibody that binds to PD-1 and prevents such immune tolerance. Several recently published clinical trials confirmed the clinical efficacy of single agent Nivolumab in pretreated patients with different cancer types. Publications on Nivolumab in Hodgkin lymphoma (HL) are very scares. The available literature is limited to only one phase 1 clinical study with 23 pretreated patients (Ansell eta l., N Engl J Med 2015;372:311-9). Case description: We report on a 30 year-old man with stage IVB HL. He failed 9 lines of prior therapy including: ABVD, ICE, radiation, ESHAP and high dose BEAM chemotherapy and autologous stem cell transplantation, IGEV, Brentuximab vedotin,. Brentuximab and Ifosfamide, GVD and Bendamustine. The patient has multiple visceral involvement including lung and liver proven by histopathology. He was wheelchair bound (ECOG 3) and oxygen dependent. He received Nivolumab achieving a major radiological response after 4 cycles (figure 1 and 2). The lung involvement by the HL has nearly completely disappeared. The involved liver has markedly decreased in size, in addition to improvement of splenomegaly. This radiological response was associated with significant clinical improvement. The performance status improved to ECOG 1and became oxygen independent. No treatment related significant side effects were observed. Conclusion: Pre-treated HL is amenable to novel immunotherapy. Nivolumab induces clinically meaningful responses with excellent tolerance. The drug enriches our treatments options by reloading the immune system response against cancer. Further clinical studies are needed to determine the effectiveness on large patients’ cohort.