Malignant gliomas are the most common primary tumors of the central nervous system but remain clinically intractable. This has engendered substantial efforts to elucidate the molecular genetic and biologic basis of glioma formation. This review focuses on recent discoveries of the genetic aberrations that occur during the progression of gliomas. These include those that inactivate tumor suppressor genes and activate oncogenes. The biologic consequences of such genetic changes on various tumor cell-host environment interactions are also described.