Simple Summary The translocator protein (TSPO) has been under extensive investigation as a specific marker in positron emission tomography (PET) to visualize brain lesions following injury or disease. In recent years, TSPO is increasingly appreciated as a potential novel therapeutic target in cancer. In Glioblastoma (GBM), the most malignant primary brain tumor, TSPO expression levels are strongly elevated and scientific evidence accumulates, hinting at a pivotal role of TSPO in tumorigenesis and glioma progression. The aim of this review is to summarize the current literature on TSPO with respect to its role both in diagnostics and especially with regard to the critical hallmarks of cancer postulated by Hanahan and Weinberg. Overall, our review contributes to a better understanding of the functional significance of TSPO in Glioblastoma and draws attention to TSPO as a potential modulator of treatment response and thus an important factor that may influence the clinical outcome of GBM. Glioblastoma (GBM) is the most fatal primary brain cancer in adults. Despite extensive treatment, tumors inevitably recur, leading to an average survival time shorter than 1.5 years. The 18 kDa translocator protein (TSPO) is abundantly expressed throughout the body including the central nervous system. The expression of TSPO increases in states of inflammation and brain injury due to microglia activation. Not least due to its location in the outer mitochondrial membrane, TSPO has been implicated with a broad spectrum of functions. These include the regulation of proliferation, apoptosis, migration, as well as mitochondrial functions such as mitochondrial respiration and oxidative stress regulation. TSPO is frequently overexpressed in GBM. Its expression level has been positively correlated to WHO grade, glioma cell proliferation, and poor prognosis of patients. Several lines of evidence indicate that TSPO plays a functional part in glioma hallmark features such as resistance to apoptosis, invasiveness, and proliferation. This review provides a critical overview of how TSPO could regulate several aspects of tumorigenesis in GBM, particularly in the context of the hallmarks of cancer proposed by Hanahan and Weinberg in 2011.