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The review highlights the recent advances in the pathogenesis, diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL).The incidence of AIDS-PCNSL has decreased in the era of highly active antiretroviral therapy (HAART). The prognosis has improved and this most probably in relation both with the HAART-induced immunologic status recovery and subsequently the possibility to use more aggressive treatment strategies. Immunomodulatory effect of HAART seems also to have an indirect antitumor activity on the disease.The treatment strategy for AIDS-PCNSL in the HAART era tends to become similar to that of the immunocompetent population. In the absence of randomized trials devoted to AIDS-PCNSL, most current national comprehensive cancer network guidelines recommend the use of high-dose methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as initial treatment in addition to HAART. The objective for the future would be that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients with special attention to systemic and neurocognitive tolerance of the treatments.