Glioblastoma multiforme (GBM) is a highly aggressive and devastating brain tumor characterized by poor prognosis and high rates of recurrence. Numerous therapeutic strategies and delivery systems are developed to prolong the survival time. They exhibit enhanced therapeutic effects in animal models, whereas few of them is applied in clinical trials. Taking into account the drug-resistance and high recurrence of GBM, combined-therapeutic strategies are exploited to maximize therapeutic efficacy. The combined therapies demonstrate superior results than those of single therapies against GBM. The co-therapeutic agents, the timing of therapeutic strategies and the delivery systems greatly affect the overall outcomes. Herein, the current advances in combined therapies for glioblastoma via systemic administration are exhibited in this review. And we will discuss the pros and cons of these combined-therapeutic strategies via nanotechnology, and provide the guidance for developing rational delivery systems to optimize treatments against GBM and other malignancies in central nervous system.