Abstract Central Nervous System (CNS) involvement in lymphoma can occur whether at diagnosis or, more often, at the progression or recurrence of disease and the most frequent clinical manifestation is lymphomatous meningitis (LM). The first risk factor for LM development is the histotype, with the highest incidence for highly aggressive non-Hodgkin's lymphomas (NHL) such as Burkitt's lymphoma (BL) and lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and the lowest for indolent NHL. LM prophylaxis in aggressive NHL (other than BL and LBL/ALL) is a much debated question, because the identification of specific risk factors remains controversial. Moreover, there is not a consensus if the LM prophylaxis should consist of systemic chemotherapy (CT), intrathecal (i.t.) CT or both. In case of LM, the i.t. CT has a key role, but there is not a consensus on treatment schedule. Newer intensified regimens and rituximab lead to reconsider the whole approach to LM.