Leptomeningeal metastasis is a common complication of cancer. Often the diagnosis can be difficult, but early diagnosis and aggressive treatment can prevent irreversible neurologic deficits. Diagnosis is usually established by the demonstration of malignant cells in the cerebrospinal fluid (CSF) or by the presence of enhancing tumor nodules on cranial or spinal MRI. Treatment may require focal radiotherapy to symptomatic sites accompanied by chemotherapy. Intra-CSF chemotherapy requires normal CSF flow dynamics and is typically limited to the use of methotrexate, cytarabine or thiotepa. Intrathecal chemotherapy is rarely efficacious, except for hematopoietic neoplasms and, to a lesser extent, breast cancer. Increasingly, systemic chemotherapy is recognized as efficacious in the treatment of leptomeningeal metastasis in part because it has the ability to penetrate into bulky disease seen on neuroimaging. The optimum choice of therapy depends upon a thorough assessment of the neurologic extent of disease, which should include complete neuraxis imaging. Patients with extensive bulky disease may be best treated with systemic chemotherapy, whereas those with a positive CSF cytology but negative imaging may be treated with intrathecal chemotherapy and spared the systemic toxicity of intravenous drug. Despite vigorous therapy, many patients do poorly and the median survival is only about four months. Nevertheless, some patients, particularly those with leukemia, lymphoma, and breast cancer, respond and a substantial minority will be alive one to two years after diagnosis.