The methylhydrazine derivative Procarbazine (PCZ) as monotherapy or in combination with CCNU and vincristine (PCV) was evaluated in a vast number of clinical trials and is still used in patients with high-grade and low-grade gliomas. The compound is an antineoplastic agent with multiple sites of action. It inhibits incorporation of small DNA precursors, as well as RNA and protein synthesis. PCZ can also directly damage DNA through an alkylation reaction. The drug is not cross-resistant with other mustard-type alkylating agents. As PCZ was in almost all trials used in a combination with CCNU and Vincristin, the efficacy can only be evaluated in the view of the PCV regimen. The published data suggest a role of PCV as a salvage regimen, especially in oligodendroglial tumors; however, well designed studies with high evidence are rare in all entities. This article summarizes the existing data with the goal to define the role of PCZ/PCV in modern neurooncology.