AIDS-lymphoma is a heterogeneous disease that most likely results from the complex interaction of several contributing factors, including chronic antigenic activation of B lymphocytes, dysregulated cytokine and co-stimulatory networks, infection with potentially oncogenic viruses (human herpesvirus-8 [HHV-8], Epstein-Barr virus), and accumulation of secondary genetic mutations. Cytokines are believed to play an important role in the immunologic decline that favors opportunistic infection and malignancy in advanced HIV infection. Recent work has provided some evidence that cytokine therapy can partially reverse the immune dysregulation seen in AIDS. This suggests that cytokines are likely to have an important role in both the pathogenesis and treatment or prevention of AIDS-lymphoma.