Abstract: Primary central nervous system lymphoma (PCNSL) is a rare disease, and no standard treatment currently exists for it. Radiotherapy alone is subjected to high recurrence and short overall survival. Radiotherapy should be applied after chemotherapy. Whole-brain radiotherapy plus chemotherapy can prolong progression-free survival and overall survival, but simultaneously result in higher incidence of neurotoxicity. For elderly patients who are prone to neurotoxicity, the suggested option is chemotherapy alone. By contrast, radiotherapy could be the second-line option for younger patients. Chemotherapy based on high-dose methotrexate has become the first-line therapy of PCNSL, and cytarabine is one of the most common components in the combination regimens. Younger patients could choose intensive regimens including new drugs, such as procarbazine and temozolomide. Temozolomide is a promising drug in elder patients with PSNSL. No consensus currently exists on cerebrospinal fluid prophylaxis in PCNSL. High-dose chemotherapy followed by autologous stem cell transplantation was also recommended in novo or refractory and recurrent PCNSL. Surgery is usually used for the diagnosis of PCNSL. Glucocorticoids should be strictly avoided prior to biopsy.