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Over the past decades, there has been an increasing use of molecular biology and genetic approaches in the assessment and management of adult gliomas, overall improving our understanding of the disease biology and behavior. Despite of these advances, maximal therapeutic intervention, as well as numerous new drugs entering clinical trials, the prognosis of malignant gliomas remains dismal. In this review, we provide an overview of the recent advances in the classification system, major molecular aberrations relevant to the biology of malignant gliomas, and standard as well as experimental treatment strategies. In addition, we discuss the complexity of this deadly disease, emphasizing the challenges associated with the enormously high degree of heterogeneity including cellular hierarchies at the inter- and intra-patient level.