Advancements in understanding the molecular alterations in DLBCL have paved the way for targeted therapies. This section discusses potential targeted therapies and their implications for HIV-associated DLBCL treatment. DLBCL is a significant health concern among PLWH, and the interplay between HIV infection, co-infections, chronic inflammation, and immune dysregulation contributes to its pathogenesis. By elucidating the mechanisms underlying DLBCL development in the HIV environment and implementing appropriate therapeutic approaches, we can improve patient outcomes and enhance the management of DLBCL in this population. Advances in understanding the intricate relationship between the HIV environment and DLBCL have provided valuable insights into the pathogenesis and management of this lymphoma subtype. Further research is needed to elucidate the mechanisms underlying DLBCL development in PLWH, identify novel therapeutic targets, and optimize treatment strategies. By addressing the unique challenges posed by the HIV environment, we can improve outcomes and quality of life for PLWH with DLBCL.