The milestones of glioblastoma (GBM) treatment are surgical resection—as large and safe as possible—and concurrent radiochemotherapy followed by adjuvant chemotherapy with temozolomide (TMZ). Chemoradiation prolongs progression-free survival (PFS) and overall survival (OS). In particular, in the phase III trial by Stupp et al., the median overall survival (OS) was 14.6 months for radiotherapy plus temozolomide versus 12.1 months for radiotherapy alone. Moreover, in the long-term analysis of the trial, the presence of the MGMT promoter methylation was a strong predictor of better outcome in the group of combined radiochemotherapy versus radiotherapy alone. For this reason, standard post-surgical treatment consist of conformal radiation therapy (60 Gy over 6 weeks) with concomitant TMZ (75 mg/m2), followed by 6–12 cycles of maintenance temozolomide (150–200 mg/m2 for 5 days every 28 days). However, despite these interventions, ultimately tumor recurrence will occur. Recently, new treatments have been proposed, which might help to address the limitations of current therapies. In this chapter, we will discuss more in detail the role of adjuvant therapies in the treatment of newly diagnosed GBM patients, with a special focus on highlighting cutting-edge technologies and new treatment modalities.