Diffuse large B-cell lymphoma (DLBCL) is the most common form of high-grade non-Hodgkin lymphoma. While treatment with immunochemotherapy has generally shown good outcomes, specific subgroups of patients with high-risk disease have an unfavorable prognosis. Extensive efforts have been made to improve outcomes in these patients. As such, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become the new standard of care for patients with relapsed or refractory DLBCL after at least two prior lines of therapy. It is an exciting new therapeutic intervention that is integral to the concept of personalized medicine.