Objectives. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by substantial clinical, genetic, and biological heterogeneity. This review aims to summarize recent advances in the management of DLBCL, both in the frontline setting and in relapsed/refractory disease, and to highlight the unmet clinical needs that persist despite therapeutic progress. Methods. A comprehensive literature review was conducted using medical databases including PubMed, HINARI, and Google Scholar. The analysis focused on randomized clinical trials, systematic reviews, and current treatment guidelines evaluating standard regimens and emerging therapies for DLBCL, particularly in first-line therapy and relapse management. Results. The R-CHOP regimen has remained the frontline standard for over two decades, with limited improvements in outcomes. However, the incorporation of polatuzumab vedotin into the R-pola-CHP regimen has demonstrated superior progression-free survival and event-free survival compared to R-CHOP in newly diagnosed patients. In the setting of early relapse or refractory disease, chimeric antigen receptor T-cell (CAR-T) therapies such as axicabtagene ciloleucel and lisocabtagene maraleucel have shown greater efficacy than autologous stem cell transplantation (ASCT), offering durable responses in selected patient populations. Conclusions. While novel therapeutic strategies have improved outcomes for certain subsets of patients with DLBCL, a significant proportion still experience treatment failure or relapse. These challenges underscore the ongoing need for research into more effective, individualized treatment approaches to optimize long-term disease control and survival.