Local invasive infiltration and growth are key features in glioblastoma, which are accompanied by remodeling of the vasculature and the destruction of the surrounding normal brain tissues. The local and regional spread of glioblastoma is often associated with poor prognosis. The invasive character of glioblastoma appears to depend partly on the proteolytic destruction of the extracellular matrix components. In this article, we review the role of proteolytic enzymes, urokinase-type plasminogen activator and matrix-metalloproteases, for diffuse infiltrative growth of glioblastoma. An understanding of the mechanisms of increased expression of these molecules in glioblastoma might provide an insight into the regulatory pathway of cellular invasion and for a new therapeutic strategy for glioblastoma.