All adult patients with Burkitt lymphoma or lymphoblastic lymphoma should receive central nervous system (CNS)-directed therapy with both intrathecal and high-dose systemic chemotherapy. There is no evidence to support the routine use of prophylactic CNS-directed therapy in any specific subgroup of adult patients with 'low grade' lymphomas. There are some anatomical sites where involvement by lymphoma is associated with a higher risk of CNS relapse. These probably include testis, breast, paranasal sinuses and the epidural space. Multivariate analyses strongly support a raised serum lactate dehydrogenase level and the involvement of more than one extranodal site as the strongest predictors of subsequent CNS relapse. A high International Prognostic Index score may replace the use of the above two factors in combination. There is evidence of good efficacy when intrathecal chemotherapy and high-dose systemic chemotherapy are used in combination. It is not clear how the best balance between the 'sensitivity' and 'specificity' of the choice of patients to receive CNS-directed therapy can be achieved.