**1. Introduction**

Malignant gliomas remain associated with poor prognosis and the cause of significant morbidity. In 2010, there was excitement that recent spectacular advancements in our basic understanding of their molecular pathogenesis, angiogenesis and new gene transfer technol‐ ogies will turn the tide in our favor. The negative results of several costly phase III clinical trials are sobering; unfortunately, they take us back to the drawing board in terms of how we can improve our methods and why brain cancer has this incredible ability to resist therapy. This chapter is organized as follows. We start by an overview of the classification and signif‐ icance of malignant gliomas. We proceed to reviewing the molecular pathogenesis of angio‐ genesis and the development of new treatment modalities against anti-angiogenesis targets, some of which were tested in Phase III clinical trials. Before considering immunotherapy strategies and targets for malignant gliomas, we review basic concepts in immunology and discuss the unique immunological features of the central nervous system (CNS). Finally, we discuss gene therapy vectors, strategies, and clinical trials in malignant gliomas. We conclude by an analysis of our current limitations, possible tumor mechanisms for resisting treatments, and what we can do to improve the outcome.

© 2014 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
