Diffuse Large B-cell Lymphoma (DLBCL) is a heterogeneous group of lymphomas characterized by rapid tumour growth and diverse clinical presentations. This section provides an introduction to DLBCL, its classification, and its association with HIV infection. The incidence of DLBCL is significantly higher in PLWH compared to the general population. This section explores the epidemiological data and highlights the increased risk of DLBCL in the HIVinfected population [1,2]. HIV infection is often accompanied by co-infections, such as Epstein-Barr Virus (EBV) and Human Herpesvirus-8 (HHV-8), which contribute to lymphomagenesis. Chronic inflammation resulting from immune dysregulation also plays a crucial role in DLBCL development. This section discusses the impact of co-infections and chronic inflammation on the pathogenesis of DLBCL.