Glioblastomas are highly malignant primary brain tumors with one of the worst survival rates among all human cancers. With a more profound understanding of the cellular and molecular mechanisms of tumor initiation and acquired resistance to conventional radio- and chemotherapy, novel therapeutic targets might be discovered to optimize therapeutic approaches. In this regard, the identification of a small cellular subpopulation, called glioblastoma stem cell or stem-like cells or glioma-initiating cells or brain tumor propagating cells, has gained attention. In this article, we briefly summarize the current state of knowledge about this tumor cell population and discuss future directions for basic and clinical research.