Neoplastic meningitis (NM) occurs in 5% to 8% of cancer patients, commonly as an end-stage process in previously metastatic disease. As newer therapeutics extend patient survival by maintaining long-term control of systemic malignancies, the incidence of NM is likely to rise. This can be expected both because of a change in the natural history of the underlying disease and the generally poor penetrance of many newer anticancer drugs into the central nervous system, thereby creating a sanctuary site for malignant cells. Currently available treatments have provided limited benefit in overall survival in NM, although long-term survival does occur. Because of the morbidity occasionally associated with treatment, prognostic indicators are being analyzed to identify patients who may benefit from systemic and/or intrathecal therapy before making the decision to initiate treatment. Additionally, because of the relative insensitivity of traditional cerebrospinal fluid analysis, new markers of NM are being investigated. This endeavor is being aided by ongoing research into the underlying biology of the metastatic process.