Malignant gliomas are the most common primary brain tumors in adults; they include 78% of all primary malignant brain tumors. The efficacy of current multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against the malignant cells. The prognosis in patients affected by primary brain tumors is still very unfavorable. Late diagnosis and the limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent, are major challenges of glioma treatment. The difficulty in overcoming the blood–brain 186barrier is one of the biggest obstacles for the delivery of chemotherapeutics. Nanotechnology-based drugs that can cross the blood–brain barrier and carry drugs or genes targeted against brain tumors could revolutionize the therapy of malignant gliomas. Nanotechnology has quickly found its application in clinical methodologies including imaging, diagnostic, and therapeutics. Nanoparticle systems are versatile and provide prolonged drug delivery directly to the tumor following direct intracerebral injection or by functionalizing the material surface with peptides and ligands allowing the drug-loaded material to be specifically targeted to the tumor. In this chapter, we describe the principal applications of nanomedicine in malignant gliomas and discuss various preclinical and/or clinical studies used to treat these aggressive brain tumors.