Glioma cells use intermediate levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for growth and invasion, and suppressing these reactive molecules thus may compromise processes that are vital for glioma survival. Increased oxidative stress has been identified in glioma cells, in particular in glioma stem-like cells. Studies have shown that these cells harbor potent antioxidant defenses, although endogenous protection against nitrosative stress remains understudied. The enhancement of oxidative or nitrosative stress offers a potential target for triggering glioma cell death, but whether oxidative and nitrosative stresses can be combined for therapeutic effects requires further research. The optimal approach of harnessing oxidative stress for anti-glioma therapy should include the induction of free radical-induced oxidative damage and the suppression of antioxidant defense mechanisms selectively in glioma cells. However, selective induction of oxidative/nitrosative stress in glioma cells remains a therapeutic challenge, and research into selective drug delivery systems is ongoing. Because of multifactorial mechanisms of glioma growth, progression, and invasion, prospective oncological therapies may include not only therapeutic oxidative/nitrosative stress but also inhibition of oncogenic kinases, antioxidant molecules, and programmed cell death mediators. • Oxidative and nitrosative stress may contribute to the mechanisms of gliomagenesis. • Antioxidants may play a leading role in anti-glioma therapy by suppressing free radicals-dependent signal transduction in glioma cells. • The dominant therapeutic approach is to enhance oxidative/nitrosative stresses to a level that is sufficient to trigger glioma cell death due to oxidative/nitrosative damage. • Promising selective combined therapies include anti-neoplastic agents and modulators of glioma cell redox status such as hyperbaric oxygenation. [ABSTRACT FROM AUTHOR]