Glioblastoma is the most frequent malignant brain tumor and is characterized by poor prognosis, increased invasiveness, and high recurrence rates. Standard treatment for glioblastoma includes maximal safe surgical resection, radiation, and chemotherapy with temozolomide. Despite treatment advances, only 15-20% of glioblastoma patients survive to 5 years, and no therapies have demonstrated a durable survival benefit in recurrent disease. In the last 10 years, significant advances in knowledge of the biology and molecular pathology of the malignancy have opened the way to new treatment options. Clinical management of patients (pseudo-progressions, side effects of therapies, best supportive care, centralization in expertise care centers) has improved. In brain tumors, such as in other solid tumors, we have entered an era of immune-oncology. Immunotherapy seems to have an acceptable safety and tolerability profile in the recurrent setting and is under investigation in clinical trials in newly diagnosed glioblastoma patients. This review focuses on novel targeted therapies recently developed for the management of newly diagnosed and recurrent glioblastomas.