The management of relapsed and refractory classical Hodgkin lymphoma (cHL) is evolving quickly owing to a range of novel agents and new therapeutic combinations under investigation, particularly in the second-line setting. These treatments can have less substantial toxic effects and more convenient administration schedules than standard inpatient chemotherapy. For patients with biopsy-proven relapsed disease, the typical strategy is to use a different treatment than the initial regimen to induce remission, followed by high-dose chemotherapy and autologous stem-cell transplant (ASCT). Randomized clinical trials have not been extensively conducted in this scenario; therefore, no second-line regimen has been established as superior. Conventional treatment is multiagent chemotherapy. Newer data exist for brentuximab vedotin (BV) alone or in combination with chemotherapy.1,2 For patients who do not reach a complete response (CR) or relapse after ASCT, the checkpoint inhibitors nivolumab and pembrolizumab represent a novel and promising therapeutic approach.3-5 These immunotherapies are beginning to be used earlier in the sequence for nontransplant candidates. We outline the strategies we use when patients with cHL do not respond adequately to or relapse after initial therapy (Figure).