Despite the success of modern therapy for Hodgkin lymphoma (HL), about 15 % of patients will fail both first-line and second-line therapy and treatment options for these patients are limited. New agents are needed to improve the outcome for relapsed or refractory HL and to improve the toxicity of current front-line regimens. Brentuximab vedotin (BV) was recently approved for HL and is likely to have a tremendous impact on the current treatment paradigm for HL. Additional agents that have demonstrated activity in HL include histone deacetylase inhibitors, such as panobinostat, entinostat, and mocetinostat, PI3-kinase/Akt/Mtor pathway inhibitors, such as everolimus, as well as lenalidomide and bendamustine. Studies evaluating these agents alone or in combination with either chemotherapy or other targeted agents are ongoing. Current challenges in HL research include identifying the most appropriate drug combinations of new and old drugs and identifying predictors of response to the new targeted agents.