Today, there is increasing evidence that PPARgamma agonists, including thiazolidinediones (TDZs) and nonthiazolidinediones, block the motility and invasiveness of glioma cells and other highly migratory tumor entities. However, the mechanism(s) by which PPARgamma activators mediate their antimigratory and anti-invasive properties remains elusive. This letter gives a short review on the debate and adds to the current knowledge by applying a PPARgamma inactive derivative of the TDZ troglitazone (Rezulin) which potently counteracts experimental glioma progression in a PPARgamma independent manner.