Open AccessThe tyrosine kinase receptor epidermal growth factor receptor (EGFR) can be activated by several ligands, thus triggering downstream pathways regulating cell growth and survival. Its dysregulation is particularly important for the development and progression of astrocytomas. After the description of its role in glioblastomas (WHO grade IV astrocytomas), an overview on the therapeutic strategies targeting EGFR is provided. It analyzes the past and ongoing trials concerning the small molecule tyrosine kinase inhibitors, i.e. gefitinib, erlotinib and the combination therapies, the EGFR vaccination strategies, the antibodies directed against EGFR and finally the intracranially administered EGFR-targeted therapies. As our understanding of the underlying molecular aberrancies in glioblastoma grows, our ability to better target specific subtypes of glioblastoma should improve. Molecular biomarker enriched clinical trials may lead to improved patient outcomes.