Mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in glioblastoma. Enhanced activation of EGFR can occur through a variety of different mechanisms, both ligand-dependent and ligand-independent. Numerous evidence has suggested that EGFR is overexpressed in most of primary glioblastomas and some of the secondary glioblastomas and is characteristic of more aggressive glioblastoma phenotypes. Additionally, recent studies have revealed that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants induced a substantial upregulation of Fyn expression. Furthermore, it was determined that Fyn expression is upregulated across a panel of patient-derived glioblastoma stem cells (GSCs) relative to normal progenitor controls. Moreover, researchers are continuously involved in elucidation of novel mechanism linking EGFR EGFR-expressing glioblastoma. The present review highlights current aspects of EGFR receptor in glioblastoma and concludes that the concept of EGFR signaling and related receptors and associated factors is evolving, however, it needs detailed evaluation for future clinical applications in cancer patients.