The HDAC4/MEF2-mediated suppression of BBB structural integrity provides the rationale for therapy of GBM with HDAC4-specific inhibitors, that may un-repress the expression of BBB-specific proteins, decrease BBB “leakage”, induce “vascular normalization”, and reverse (or bypass) the mechanisms of resistance to VEGFR inhibitors (i.e., bevacizumab). This evidence concerns the gene HDAC4 and glioblastoma.