Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of patients with diffuse large B-cell lymphoma (DLBCL) who are refractory or relapse after immunochemotherapy. This strategy consists in genetically modifying the patient's own T lymphocytes to favor the recognition of selected tumor antigens. Currently, we have two anti-CD19 CAR-T drugs approved in Spain for patients with DLBCL after two or more prior treatment lines and there are multiple ongoing clinical trials exploring earlier lines of treatment. Both clinical trials and post-marketing real-world data have contributed to better define the efficacy and safety profile of each construct, identifying the main prognostic response factors and improving the management of each step in this therapy. All these aspects are reviewed herein.