Glioblastoma multiforme are mortifying brain tumors that contain a subpopulation of tumor cells with stem-like properties, termed as glioblastoma stem-like cells (GSCs). These GSCs constitute an autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. A new therapeutic strategy would consist of targeting the GSC population. The GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells thereby involved in bidirectional molecular and cellular interactions. In this scenario, the endothelium not only supplies oxygen and necessary nutrients but also seeds a protective microenvironment for tumor growth. Although GSC fate, plasticity, and survival are regulated by external cues emanating from endothelial cells, the nature of such angiocrine signals remains unknown. Our laboratory conclusively demonstrated that brain endothelial cells positively control the expansion of GSCs. Notably, we found that GSCs are addicted to the hormonal peptide apelin (APLN) secreted by surrounding endothelial cells, and identified the APLN/APLNR nexus as a promising druggable network in glioblastoma.