© 2006 by Taylor & Francis Group, LLC. This chapter updates previous knowledge on cytokine expression in tumors of the central nervous system (CNS) and adds information relating to specific cytokine receptors and their cognate ligands as possible targets for brain tumor therapeutic modulation [1,2]. Due to space constraints, we focused our discussion and cited references mostly on work done in the last 10 years. Further readings on cytokine expression in relation to normal brain physiology and pathology can be found in other chapters of this book. Lastly, we discuss the potential of intracellular targeting of nonredundant “bottleneck” signaling events within the stromal and tumor microenvironment for more efficacious therapeutic activity in vivo.