Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, with high heterogeneity in molecular genetics, immunophenotype, and clinical prognosis. R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) is the standard treatment for DLBCL. In recent years, the way to improve the therapeutic effect of DLBCL have been thoroughly investigated. In 2015, the American Society of Clinical Oncology proposed the R-CHOP+X treatment strategy, defined as RCHOP plus another drug (X) based on cell origin classification; however, these treatment strategies failed successively. The future direction of DLBCL treatment may involve screening for different DLBCL subgroups and administering individualized targeted therapies based on more precise stratification methods than previously available. In addition, immunotherapy with antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells(CAR-T), among others, has greatly progressed in recent years, bringing new hope to patients with DLBCL. In this review, we discuss the latest advances in DLBCL targeted therapies that are based on precise stratification, immunotherapy, and the latest genetic testing methods.