This article briefly reviews the basic research findings on brain tumors made in the last decade and how they are now impacting clinical trials. Major improvements in our understanding of the genetic, molecular, and biological mechanisms that lead to brain tumor development have been made. These include mechanistic insights on how tumor cells overcome cell cycle control, evade programmed cell death, induce blood vessel formation, and escape immune regulation. These advances have been tremendously accelerated by the availability of novel whole-genome analysis technologies. These findings are now being translated into innovative clinical trials that provide new hope for patients with these devastating diseases.