Primary central nervous system lymphoma is a stage 1E non-Hodgkin's lymphoma confined to the nervous system. It is seen in immunocompetent and immunodeficient populations, the latter group associated with the Epstein-Barr virus. Primary central nervous system lymphoma can affect the brain, leptomeninges, spinal cord or eyes. The institution of high-dose methotrexate-based regimens and whole-brain radiation therapy has significantly increased survival, but neurotoxicity is high in patients over 60 years of age. Despite these advances, 50% of patients initially treated will relapse. Recent investigations include the use of rituximab (immunotherapy) and stem-cell transplantation, as well as regimens without whole-brain radiation therapy in the elderly. The optimal treatment regimen is yet to been determined.