Despite a growing therapeutic arsenal to treat relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), outcomes remain poor. Only approximately half of patients with this disease are eligible to receive curative autologous stem cell transplant, and of those, only half will be cured. Moreover, for patients who are transplant-ineligible, there are few effective options. Dr. Matthew J. Matasar discussed the current unmet needs in the treatment of patients with R/R DLBCL, treatment strategies in the second- and third-line settings, and emerging therapeutic options.