Primary central nervous system lymphoma is a quite infrequent disease within lymphoproliferative disorders. Moreover, it must be taken into account that, even considering the progressive spreading of ameliorated diagnostic tools and skills, histology remains the hinge of a correct diagnosis (stereotactic cerebral biopsy). Hence, randomised clinical protocols with a sufficiently large number of patients enrolled are difficult to perform and a generalized consensus on the best therapeutic options is hard to achieve. In this article, the more frequent practical and clinical aspects regarding diagnosis and staging of this rare disease are discussed. Furthermore, we analyze the different therapeutic options that were considered in a relatively recent past in which the median survival from diagnosis was not longer than a year, working down the pathway to the present and, finally, to the near future, always considering both first line and salvage therapy.The goal remains to optimize and standardize the therapeutic approach in order to achieve a generalized consensus that should lead to better overall clinical results.