The prognosis of patients with diffuse large B-cell lymphoma a primary refractory disease or relapsed within 12 months after autologous hematopoietic cell transplantation is poor with a median survival of only 6 months. With the new CD19-directed CAR T-cell therapy, 40% of the patients still achieve a long-term remission. However, this new treatment does bring new challenges such as bridging the time during the CAR T-cell product time, and recognition of treatment-related side effects such as cytokine release syndrome or neurotoxicity. Therefore, treatment by a dedicated, multidisciplinary team is necessary. Future research will focus on extending CAR T-cell therapy to other diseases and improve treatment in non-responsiveness or resistance to CAR-T cell therapy.