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Earlier, prior to the development of effective systemic therapy, monotherapy with whole-brain radiotherapy (WBRT) was widely used to treat primary central nervous system lymphoma (PCNSL). Recently, chemotherapy, especially with high dose methotrexate (HDMTX), has largely replaced WBRT as upfront treatment, and the most accepted standard of care is induction with a combination drug therapy followed by consolidation therapy with either autologous stem-cell transplantation (ASCT) or radiation. Whilst WBRT is an effective component of treatment, it is occasionally associated with risk of permanent, irreversible neurotoxicity when doses of more than 30 Gy are used. Hence, there has been a strong focus on the optimization of radiotherapy (RT) which includes dose reduction in the consolidation phase. In this comprehensive review, we have summarized the progress on clinical results and evidence considering the role and use of radiation including combined treatment modalities, low-dose radiotherapy, and neurotoxicity. Finally, we present a practical approach to low-dose WBRT and boosting higher doses to the gross tumor that can be integrated into clinical practice.