Despite the extensive research efforts over the past century, glioblastoma multiforme (GBM) remains an ominous diagnosis leading fast to progressive disability and death despite the aggressive treatment including microsurgical resection, chemotherapy, radiotherapy and stereotactic radiosurgery. Advanced neuroimaging techniques, such as volumetric acquisitions, spectroscopy, diffusion and perfusion studies added to conventional imaging, provide in selected cases a non-invasive alternative to pathological diagnosis but they are also precious tools to define the boundaries of image-guided microsurgical resection and/or radiosurgical ablation. This paper reviews the role of advanced neuroimaging techniques in the diagnosis and treatment of GBM.