Metastasis to the central nervous system (CNS), including neoplastic meningitis (NM), is a devastating complication of systemic cancer. With the improved survival of cancer patients, the incidence of CNS metastasis is rising, especially among those with breast or lung carcinoma. New therapies that effectively treat these primary tumors outside of the CNS have underscored the significance of CNS metastases; they have become a significant clinical issue and a therapeutic challenge. This review discusses clinical situations in which treatment or chemoprophylaxis of CNS metastases and NM from breast or lung cancer may play an important role. Potential clinical trials to assess these assumptions also will be proposed.