Hodgkin lymphoma (HL) is a B-cell malignancy that typically has a favorable prognosis when treated with chemotherapy, often in combination with radiation therapy. The prognosis for patients whose disease relapses or is refractory, however, is far less favorable and novel therapies are needed for these patients. The unique cellular composition of HL provides a number of opportunities to target either the malignant Reed-Sternberg cell or the inflammatory tumor microenvironment. Antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints, have all demonstrated activity in HL. Current and future trials are exploring the use of these agents in combination with each other and with standard chemotherapy.