Diffuse large B-cell lymphoma (DLBCL) is biologically aggressive and most common pathological type of non-Hodgkin's lymphoma (NHL), and about one-third of these patients are refractory or relapsed ultimately. Based on the molecular heterogeneity, DLBCL can be divided into 3 main molecular subtypes: germinal center B-cell like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL). Arising from B cells at distinct stages of differentiation, these subtypes are also diverse in mechanisms of oncogenic activation. So targeting specific oncogene addictions within the DLBCL subtypes offers a more-precise approach to therapy in comparison with the traditional chemotherapies, undoubtedly bringing a bright hope for the treatment of relapsed/refractory DLBCL. In this article, the advances in diagnosis and therapy of GCB-DLBCL, ABC-DLBCL and PMBL relapsed/refractory diffuse large B-cell lymphoma are summarized.