The molecular elucidation of epigenetic processes underlying both the physiological and pathological aspects of cellular behavior is gaining growing interest in the biomedical research field. This chapter tackles the most recent findings in the field of epigenetic mechanisms implicated in glioma. Glioma, a cancer of the glial cells, makes up over 30% of all brain and central nervous system tumors, and 70% of all malignant brain tumors. The main focus herein will be directed toward discerning epigenetic changes of nuclear DNA, mitochondrial DNA, and histone through methylation, one of the processes that is closely implicated with gliomagenesis. Moreover, the correlation between genetic disruption and epigenetic machinery is underscored, represented by mutations within isocitrate dehydrogenase genes IDH1/2. Finally, the numerous conventional therapeutics as well as novel nanotherapeutic approaches taken against distinct epigenetic targets will be discussed.