Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults, exhibiting high mortality. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has only limited effectiveness. The progress in genomics regarding GBM, in the detection of new markers of oncogenesis, abnormalities in signalling pathways, tumor microenvironment, and pathological angiogenesis over the past decade are briefly discussed. The role of novel prognostic in this review biomarkers [isocitrate dehydrogenases 1 and 2, CpG island methylator phenotype, promoter methylation status of the MGMT (O-6-methylguanine-methyltransferase) gene] is also discussed. New targeted therapeutic approaches are classified into several functional subgroups, such as inhibitors of growth factors and their receptors, inhibitors of proteins of intracellular signaling pathways, epigenetic gene-expressing mechanisms, inhibitors of tumor angiogenesis, tumor imunotherapy and vaccines. Finally novel possibilities for GBM treatment are summarized in this review.