Evaluation of Central Nervous System (CNS) focal lesions has been classically made focusing on the assessment solid or enhancing component. However, the assessment of solitary peripherally enhancing lesions where the differential diagnosis includes High-Grade Gliomas (HGG) and metastasis, is usually challenging. Several studies have tried to address the characteristics of peritumoral non-enhancing areas, for better characterization of these lesions. Peritumoral hyperintense T2/FLAIR signal abnormality predominantly contains infiltrating tumor cells in HGG whereas CNS metastasis induce pure vasogenic edema. In addition, the accurate determination of the real extension of HGG is critical for treatment selection and outcome. Conventional MRI sequences are limited in distinguishing infiltrating neoplasm from vasogenic edema. Advanced MRI sequences like Diffusion Weighted Imaging (DWI), Diffusion Tensor Imaging (DTI), Perfusion Weighted Imaging (PWI) and MR spectroscopy (MRS) have all been utilized for this aim with acceptable results. Other advanced MRI approaches, less explored for this task such as Arterial Spin Labelling (ASL), Diffusion Kurtosis Imaging (DKI), T2 relaxometry or Amide Proton Transfer (APT) are also showning promising results in this scenario. In this article, we will discuss the physiopathological basis of peritumoral T2/FLAIR signal abnormality and review potential applications of advanced MRI sequences for its evaluation.