Glioblastoma is a deadly disease that has not shown improvement despite the development of new diagnostic tools and innovative targeted therapies. This grim outcome is mainly related to a complex intra-and inter-individual heterogeneity resulting from severe genetic instability. Understanding glioblastoma biology may establish a foundation to improve prophylaxis, early diagnosis, prognosis, and treatment prediction, thus leading to a better outcome. Recent advances in technologies such as genomics, epigenomics, transcriptomics, and proteomics have led to unprecedented discoveries of potential prognostic and predictive markers. Several of these biomarkers are in deep need of validation to be used in clinical routine. In this chapter, we will discuss the most accomplished recent advances in the genomics of glioblastoma and insight into personalized medicine using validated, and not yet validated, biomarkers that may have great potential to improve patients' outcomes.