Current treatments of high grade malignant gliomas do not significantly affect patient prognosis, in large measure because they can not curtail the diffuse invasion of single glioma cells into brain tissue surrounding the tumor. Here, we investigate whether SAHA affects glioma invasion, which could be of critical import clinically. Our results show that SAHA inhibits both glioma proliferation and invasion. MTT assays show that the proliferation of C6 glioma cells is arrested after treatment with 5mM SAHA for 24 hours. A Boyden chamber invasive assay as well as a 3D variation on this assay shows SAHA inhibits C6 invasion at 5mM. Multicellular tumor spheroids embedded in 3D collagen I matrices in the presence of SAHA were also monitored via microscopy. The results show that cell invasion and volumetric spheroid growth are inhibited by SAHA even though the majority of cells within the MTS remain viable. We find that SAHA independently affects both C6 glioma invasion and the reorganization of the tumor surroundings that usually proceeds glioma cell invasion into collagen I gels. Preliminary investigation into the mechanism by which SAHA inhibits invasion was undertaken. Because degradation of extracellular matrix via matrix metalloproteases (MMPs) is likely essential for tumor invasion, we investigated whether SAHA affects MMP production. Zymography reveals that MMP2 is down-regulated by SAHA. We have shown that SAHA decreases glioma cell proliferation, ability to reorganize its surroundings, and ability to invade these surroundings.