Despite improvements in surgery, radiation- and chemotherapy the high-grade gliomas have a poor survival rate. A contributing factor to the poor survival is the inability of currently available imaging techniques to accurately delineate the tumour which results that targeted focal treatment may not be effective. Conventional imaging is not always able to grade the tumour or to give an early assessment of the effectiveness of radiation and/or chemotherapy which is a constant dilemma for the neuroradiologist. In addition, concurrent treatment with radiotherapy and chemotherapy is associated with so called pseudoprogression, reflecting treatment-induced changes in the tumour resulting in an increase in size and/or a brighter appearance than on pretreatment MRI. These transient changes often occur a couple of months after radiation treatment and they may misleadingly suggest tumour progression but are transient and eventually the tumour will stabilize in size or even shrink (1). Novel combination therapies that hamper tumour angiogenesis, for example treatment with bevacizumab, can lead to diminished edema and contrast enhancement so called pseudoresponse, with imaging findings that can cause diagnostic difficulties. Also the use of gamma knife radiation has brought about new diagnostic challenges (1-3). Gamma knife therapy is associated with a high incidence of radiation necrosis, with similar morphological characteristics as recurrent tumour. Radiation necrosis can also occur months or even later post treatment and the history and the clinical information becomes crucial for correct diagnosis. These different imaging findings in association with treatment of a brain tumour is a challenge for radiologists and often results in repeated imaging and multidisciplinary discussions. Early identification of patients who suffer from tumour recurrence can be of great advantage: it provides the opportunity to adjust individual more rapidly, and sparing patients unnecessary morbidity, and delay in initiation of other maybe more effective treatment. In recent years different functional imaging approaches such as dynamic contrast-enhanced (DCE) and dynamic susceptibility –weighted contrast (DSC) MRI, diffusion-weighted imaging, diffusion tensor imaging, and spectroscopy have been complementary used for imaging evaluation of treatment response Also the use of PET with different tracers like 18F-Fluoro-etyl-tyrosin (18FET-PET) in the differentiation between a progressing tumour and pseudo-progression and 11C-methione PET do distinguish radiation injury from recurrent tumour have shown promising results. New MR imaging biomarkers are in the horizon such as Q-space Trajectory Imaging (QTI) or so called cell-shape imaging, a method that by the use of magic-angle diffusion encoding yields an index called the microscopic anisotropy (µFA) (4). The µFA can be evaluated in the tumour core and has in a recent study demonstrated high correlation with the histopathology (4). Another potential method to further characterize the tumour pre-surgically is the Filter Exchange Imaging (FEXI) method with the apparent exchange rate (AXR) which is related to the cell membrane permeability and may play a major role in characterizing the cellular function (5,6). These new imaging biomarkers hold promises not only in pre-surgical viewing of the tumour but might have a role to play in the follow-up of treatment response and help the neuroradiologist and clinician in decision making. New challenges for the radiologist in diagnosing and grading tumours are also present especially when we look at pediatric tumours with medulloblastoma being a good example. New insights clearly define the medulloblstoma into different groups with different prognosis and different imaging characteristics based on molecular markers and genomics (7,8). Also other pediatric brain tumors such as ependymoma, low grade gliomas and atypic teratoid/rhabdoid tumour have demonstrated subgroups with different prognosis and the need for different treatment regims. In this lecture different aspect of the problems facing the radiologist when evaluating brain tumours and the possible support of advance MR imaging methods as well as new imaging biomarkers used to support pseudo-response, to differentiate between pseudo-progression or radiation injury and true tumour progression and monitoring schemes to assess early treatment response such as the parametric response maps (9,10) will be presented and discussed.