Although some patients with overt leptomeningeal cancer can now be cured, the proportion of patients who survive is very small, and the cost of cure, in terms of neuropsychological and educational morbidity, is substantial. Yet the incidence of central nervous system infiltration of systemic cancer is generally increasing, in most instances because control of systemic cancer has sufficiently prolonged survival to permit leptomeningeal metastases to develop and become symptomatic or detectable. The best chance for prolongation of life and possible cure is early detection and aggressive therapy in those forms of cancer that are amenable to therapy. We review the incidence of the various forms of leptomeningeal metastases, current concepts of pathogenesis and pathophysiology, clinical and laboratory features of leptomeningeal cancer, the available therapies, and the associated toxicities. The various methods that have been used to prevent and treat leptomeningeal cancer are described with an emphasis on childhood acute lymphoblastic leukemia (ALL) because it plays a predominant role in our understanding of meningeal neoplasms in general.