Oncology is leading disease in cancer as it is known, there is a high grade gliomas represent the main challenge for the neurooncology also that may lead for different reasons initially as tumour cells show a mostly destructive behaviour toward the normal brain tissue, making them an very difficult to target for any kind of therapy. Then, Glioblastoma Multiforme develops inside an isolated human compartment, separated from the bloodstream by the interposition of the systemic blood-brain barrier, that represent an obstacle to the diffusion of drugs into the brain for the pharmacological point of view. Despite many successes in different areas of Oncology, prognosis of Glioblastoma Multiforme did not change over the past 30 years, except for a small benefit achieved with the Stupp’s protocol. The reason of these failures could be attributed to the lack of knowledge of many different biological aspects of the tumour. Hence, it is crucial to focus the determinations to a more exact biological group of this disease, as this aspect can have important impact on the current research for new therapies.