Neoplastic meningitis (NM) is the result of the diffuse or multifocal localization of cancer cells in the cerebral spinal fluid (CSF). NM is more often a late complication of solid tumor or lymphoproliferative malignancies. At present, the goal of therapeutic strategies is palliative and the evaluation of high or low risk is important in identifying which patients could benefit from aggressive treatments such as radiation therapy and chemotherapy. Given that NM is a cancer complication that can spread throughout the entire subarachnoid space, chemotherapy, whether intrathecal or systemic, is currently considered the best treatment option, but optimal treatment is still controversial. This review summarizes intrathecal and systemic chemotherapeutic options in the treatment of NM and the related toxicities.