Glioblastoma multiforme (GB) is the most common primary malignancy of the central nervous system. GB is a highly anabolic, proliferative, infiltrative and diffuse primary brain tumor, characterized by recurrence (rGB), resistance to chemotherapy and low life expectancy of 14 months with a survival median of 12 months. Furthermore, GB is associated with different pre and postoperative treatment approaches such as surgery, radiotherapy and chemotherapy with Themozolamide (TMZ), an alkylant agent capable of methylating nucleotide bases and, as a consequence, preventing cell replication. The chemoresistance may be due to vascularization´s difficulty to deliver the drug through the blood brain barrier (BBB) or poor survival with TMZ, which leads to poor prognosis. Recently, it has been noticed the relations between high levels of homocysteine (Hcy) and severe pathologies, namely, neurodegenerative disorders , lung, colorectal and nervous tissue carcinomas. Methionine (Met) is an aminoacid derived by dietary intake and its methyl grouping pathway plays a crucial role in macromolecule synthesis, gene expression control and maintenance of cellular redox balance. Met is essential for the synthesis of Hcy by transmethylation and its pathway is closely associated with epigenetic processes, including DNA methylation.