Classical Hodgkin’s lymphoma is a highly curable disease, but 10–25% of patients with higher-risk disease relapse. The introduction of checkpoint inhibitors (CPIs) targeting PD-1 have changed the landscape of treatment for patients with relapsed/refractory disease to multiple lines of therapy. The depth of response to CPI as a monotherapy is highest in the first relapse as salvage therapy based on outcomes reported in several phase II studies. With earlier use of CPI and brentuximab vedotin, the optimal sequencing of therapy is evolving. In this review, we will summarize clinical investigation of anti-PD-1 mAb in earlier line settings to provide insights on utilizing these agents as chemotherapy- and radiation-sparing approaches, increasing depth of response, and as part of combination regimens.