Insulin-like growth factor binding protein-2 (IGFBP-2) is reported to be a modulator of the action of insulin-like growth factors (IGFs), whereas IGF-independent effects of IGFBP-2 on cellular proliferation, apoptosis, and mobility have been revealed not only during the embryonic state but also in the pathological state of cancer. As well as other types of carcinomas, overexpression of IGFBP-2 has been reported in glioblastoma multiforme (GBM), the most malignant brain tumor characterized by rapid growth, extensive invasiveness, and angiogenesis. However, it remains unclear how IGFBP-2 is involved in the malignant features of GBM. This review outlines the IGF-dependent and -independent functions of IGFBP-2 and focuses on the roles of IGFBP-2 in the progression of GBM.