In human glioblastoma patients and in orthotopic mouse models of glioblastoma, we have demonstrated that one potential mechanism of treatment failure of VEGF-targeted antiangiogenic agents is the up regulation of p-STAT3 that is associated with tumorigencity and enhanced progression that is consistent with the aggressive phenotype that has been previously described upon failure with anti-VEGF agents [3, 9, 28]. Here, STAT3 is linked to glioblastoma.