Primary central nervous system lymphoma (PCL) is an uncommon non-Hodgkin’s lymphoma located outside the lymph nodes. It usually involves the brain, soft meninges, eye or spinal cord and there is no evidence of systemic involvement. Untreated PCL progresses rapidly and usually dies within 1.5 months of diagnosis. Patient survival after whole brain radiotherapy usually increases to 12-18 months. If radiotherapy is followed by chemotherapy or chemotherapy followed by radiotherapy, the mean survival can be increased to 36-48 months. However, whole brain radiotherapy, especially in elderly patients, has a high potential for complicating symptomatic neurotoxicity. There is no most appropriate treatment option for PCL. The main treatment option for PCL is methotrexate-based induction chemotherapy, which should be recommended to patients to participate in clinical trials if possible. A uniform treatment regimen is inconclusive. Treatment includes chemotherapy, whole brain radiotherapy and high dose followed by autologous hematopoietic cell transplantation. the aim of PCL treatment is to prolong survival. For patients who decide to give chemotherapy, we recommend high-dose methotrexate-based induction chemotherapy rather than one type of whole-brain radiotherapy alone. Those patients in good general condition who do not choose to participate in clinical trials, we recommend giving methotrexate in combination with cytarabine rather than one methotrexate alone. Options for chemotherapy include: methotrexate, temozolomide, rituximab (MTR) or rituximab, methotrexate, and methylbutyrazine (R-MPV). For patients who cannot tolerate high-dose methotrexate induction therapy, chemotherapy regimens (including: temozolomide and rituximab; cytarabine and etoposide; or anti-folate agents in addition to methotrexate) or palliative regimens are available. Palliative regimens include whole brain radiotherapy or steroid hormones alone. Holistic unification: The most appropriate holistic treatment regimen is inconclusive. The options are: chemotherapy, autologous hematopoietic cell transplantation or whole-brain radiotherapy. In younger patients, who have achieved complete remission after high-dose chemotherapy, we recommend deferring radiotherapy rather than giving it immediately after the end of chemotherapy. Patients older than 60 years have a higher risk of symptomatic neurotoxicity after radiotherapy. For such patients, we recommend deferring radiotherapy until disease progression occurs, rather than giving whole-brain radiotherapy immediately after chemotherapy. Recalcitrant lymphoma: In young patients, after methotrexate-based chemotherapy has not achieved complete remission, a second chemotherapy regimen (cytarabine, etoposide) should be given, and autologous hematopoietic cell transplantation may be used as an acceptable treatment option in patients who are partially effective on initial therapy. In such patients, we also consider the administration of whole-brain radiotherapy right after the completion of chemotherapy, rather than waiting for the disease to progress again. Follow-up: After the initial planned treatment regimen is completed, the disease is not considered cured. Patients should be evaluated to see how they respond to treatment and to observe for relapses, as well as to see if there is any toxicity from the long course of treatment. Relapse: Treatment after relapse includes re-treatment with high doses of methotrexate for patients in complete remission after initial methotrexate treatment. Additional chemotherapy regimens include cytarabine and etoposide, autologous hematopoietic cell transplantation (HDT/HCT), and whole brain radiation therapy.