With increasing knowledge of cellular networks of gene and molecular interactions, and their alterations in GBM (glioblastoma multiforme), it is now possible to apply methods of Network Pharmacology (NP) to predict candidate drug targets for this malignant brain tumor. NP requires the development of mathematical methods for network stability and perturbation analysis to identify sensitive and druggable network components, as well as computational platforms to carry out in silico simulations of therapeutic interventions. This review focuses on the three most frequently deregulated GBM pathways involving membrane receptor tyrosine kinases, p53, and Rb. Structural features of these networks that may confound targeted therapies are discussed.