Glioblastoma (GBM) is the most common and most aggressive cancer of the central nervous system exhibiting dismal 5-year survival rates of 5 %. [1, 2] Currently, surgical resection (limited due to diffuse and infiltrative nature of GBM) and concomitant chemoradiotherapy offer highest median survival rates of 14 months. [3] Chemotherapy of GBM is especially challenging due to the rapid proliferative rate of GBM cells [4] , the appearance of treatment resistant cell clones shortly after initial treatment [5, 6] as well as the limited access of systemically administered agents to the brain parenchyma due to the blood-brain-barrier (BBB) [7, 8] . Despite these drawbacks, chemoradiotherapy greatly improves mean 3-year survival rates from 1.9 to 16 % compared to radiotherapy alone in the case of the most widely used chemotherapeutic agent for GBM treatment, temozolomide (TMZ). However, rapid development of TMZ resistance underline the urgent clinical need for better treatment options, potentially by using alternative active pharmaceutical ingredients (APIs) for GBM chemotherapy. [9] Statins are a family of widely used drugs for the treatment of hypercholesterolemia. They act as inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase thus being potent inhibitors of cholesterol biosynthesis. However, beyond their effects on serum cholesterol levels, recent research effort gives increasing evidence on cancer prevention and/or treatment properties of statins through interactions with essential cellular functions such as cell proliferation and differentiation. Several in vitro and in vivo studies have demonstrated tumor growth inhibition as well as induction of apoptosis in various melanoma , glioma , neuroblastoma , leukemia as well as glioblastoma cell lines . The underlying modes of action of statins causing (i) inhibition of tumor cell growth, (ii) repression of tumor metastases, (iii) inhibition of angiogenesis and (iv) induction of apoptosis were comprehensively reviewed by Hindler et al. , Pisanti et al. and Gizzo et al. [19] As cell replication of GBM is highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties, their growth is naturally highly vulnerable to statins acting as competitive inhibitors of the enzyme regulating MVA synthesis -HMG-CoA reductase. [20, 21] Furthermore, lovastatin increases the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth and differentiation thus strongly reducing glioma proliferation. Realtime PCR analysis of U87 glioma spheroids revealed that atorvastatin (ATV) induced cell apoptosis by down-regulating the expression of anti-apoptotic Bcl-2 and up-regulating apoptotic caspase-3 and caspase-8 factors. Increase in caspase-3 activity in glioblastoma was also confirmed for other statins. Investigating the Ras downstream cascade, it was found that the increase was due to a reduced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. As the activation levels of these signal transduction molecules were restored in the presence of geranylgeranyl-pyrophosphate (GGPP), the inhibition of ERK1/2 and Akt activation in C6 glioma cells was correlated to the inhibition of GGPP biosynthesis. ATV also reduced the pro-tumorigenic effects of microglia on glioma migration and invasion by reducing the microglial expression of membrane type 1 metalloproteinase (MT1-MMP). It was suggested that the down-regulation of MT1-MMP was controlled by a p38 MAPK pathway in microglia. Furthermore, ATV was suggested to decrease the expression of pro-inflammatory proteins and interleukins (IL). This is important, as inflammatory microenvironment generally promotes malignant progression which is especially true for GBM . Although not discussed in direct correlation with GBM but worth mentioning, statins have been reported to sensitize cells to ferroptosis and induce ferroptosis in selected cell lines (however, further studies are necessary to confirm this). Furthermore, combination therapy of temozolomide and ATV in combination with radiotherapy in newly diagnosed GBM patients was promising (progression free survival (PFS) rate at 6 months: 67 % and median PFS of 9.1 months), meeting criteria for continued accrual in a phase II clinical study (NCT02029573). In addition, considerable evidence suggests that statins also exhibit immunomodulatory properties, as e.g.