Central nervous system involvement with malignant lymphoma whether primary or secondary is an uncommon but not rare complication observed in the management of patients with hematological malignancy. Its importance lies in the considerable morbidity and mortality with which it is associated and the inadequacy of therapy. In Section I, Dr. Lauren Abrey addresses the totality of the problem of primary central nervous system lymphoma, with emphasis on strategies increasingly dependent on systemic chemotherapy. In Section II, Dr. John Sandlund reviews the success of sequential clinical trials of overall therapy for acute lymphoblastic leukemia in childhood, identifying those patients at high risk of central nervous system leukemia and the development of a rational therapeutic strategy for prevention. In Section III, Dr. Andrew Lister discusses the issue of secondary central nervous system involvement with lymphoma and the indications for prophylaxis.