In recent years, it has become evident that astrocytes harbor functional receptors to many neurotransmitters. including substance P (SP), an undecapeptide belonging to the tachykinin family of neuropeptides. SP is an important stimulus for reactive astrocytes in CNS development, infection and injury, and provides a link for bi-directional interactions between glial cells and neurons. In brain tumors, malignant glial cells originating from astrocytes, via NK1 receptors, are triggered by tachykinins, SP and neurokinin A (NKA), to release soluble mediators, in particular cytokines, and increase their proliferative rate. In this paper, we review the results obtained in in vitro and in vivo studies on the role of SP as an inducer of human glioma responses that may be relevant for tumor progression. In addition, the presence of SP and the expression of NK1 receptors in glioma explants have been examined. We discuss the possible use of selective NK1 receptor antagonists as a therapeutic approach to treat malignant gliomas.