Many systemic cytotoxic agents cannot penetrate the blood-brain barrier. Because of this, in approximately 5% of cancer cases, metastatic disease is seen in the leptomeninges. Without treatment, patients with neoplastic meningitis (NM) generally survive for only a matter of weeks. In the treatment of NM, intraventricular (IVT) topotecan results in progression-free and overall survival outcomes similar to those seen with other IVT chemotherapies, while being particularly well tolerated by most patients. In this article, we present the case studies of five patients with NM, with various primary malignancies, who received treatment with IVT topotecan.