Battling aggressive brain tumors represents a struggle endeavored by scientists and physicians across many different disciplines. The molecular and physiological abnormalities that accompany this fatal disease render malignant brain tumors arguably one of the most difficult pathologies to treat. For this reason, the efforts to combat this fatal disease are represented by a plethora of research. This chapter is organized to illustrate common themes in drug targeting for the treatment of brain tumors. Each section is organized based on the therapeutic approach: small molecules, local drug delivery, or biological therapy. In each subsection we discuss the rationale that has ushered each development to the 'center stage' in brain tumor therapy and provide illustrative examples using the most relevant and heretofore advanced developments. In this way, we hope to provide a discussion of brain tumor therapy that is all-encompassing yet detailed enough to give the reader a broad understanding of how researchers and clinicians attempt to improve the outcome of patients diagnosed with this debilitating disease.