Primary brain tumors are generally difficult to treat because of the unique location of the lesions. In addition, normal brain structures are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is sometimes still injured, which can leave the patient in a debilitated state. The hemodynamic and metabolic state of such peritumoral brain tissue is not yet well understood, and there are only a small number of experimental hypotheses of its reaction and changes to the growing primary brain tumor. In addition, primary brain tumors may be influenced by certain anticancer drugs, which cause oxidative stress and consecutive cell death, or by gamma-irradiation. Currently, no established diagnostic methods exist to demonstrate and/or quantify the metabolic condition of the peritumoral tissue. The therapeutic strategy for possible pharmacological neuroprotection should, in the future, still be related to metabolic parameters, as well as in the peritumor tissue to treat primary brain tumors without risk to sensitive normal tissue. To achieve this aim, there has been particular emphasis on the biological behavior of primary brain tumors and peritumor tissue, as well as the potential correlation among them. Thus, priority should be given to identifying more target antigens in primary brain tumors and defining those cells present in the brain parenchyma that are essential to maintain a neuroprotective effect. However, at this time, the postinjury enhancement of neurogenesis appears to offer the best hope for long-lasting functional recovery following surgery of primary brain tumors.