Glioblastoma is the most aggressive and the most common primary malignant brain tumor in adults. Risk factors for glioblastoma are widely elusive and the clinical course is generally fatal. Diagnosis is based on histopathological findings, but assessment of molecular markers such as isocitrate dehydrogenase (IDH) mutations and O6-methylguanyl DNA methyltransferase (MGMT) promoter methylation as well as more extensive molecular profiling is increasingly applied for prognostic subclassification and to individualize treatment approaches. Standard treatment of glioblastoma comprises the classical modalities surgery, radiotherapy, and alkylating agent chemotherapy, but molecularly targeted and immunological approaches are in clinical testing. Future challenges include the molecular dissection of spatial and temporal molecular heterogeneity.