Despite optimal clinical treatment, the prognosis for malignant gliomas remains poor. One of the primary reasons for treatment failure is not diffuse dissemination, but local invasion. Recently, there has been an increase in information regarding specific molecules that determine the aggressiveness and invasion potential of high-grade astrocytic tumors. In particular, expression of matrix metalloproteases in high-grade gliomas appears to correlate with tissue invasiveness. It is the purpose of the present review to describe the connection between alterations in growth-related genes, protease activity, and tumor biology, and how these connections may suggest potential novel therapeutic targets.