Oncolytic herpes simplex virus (HSV) is a novel therapeutic strategy to treat cancer, including in the brain.  Oncolytic HSVs are genetically engineering to selectively replicate in cancer cells and not normal cells, so they are safe to administer to patients.  They target cancer via two mechanisms; direct cancer cell killing and induction of anti-tumor immunity.  A major focus of our studies are brain tumors, especially glioblastoma, the most common primary malignant brain tumor for which there are no effective therapies.  We are developing oncolytic HSV vectors that are efficacious in the brain and representative tumor models to evaluate therapy, including cancer stem cells.  A powerful approach to enhancing efficacy is combining oncolytic HSV with other cancer therapeutics, including agents or transgenes that modulate the tumor microenvironment and anti-tumor immune responses, or by sensitizing cancer cells to chemotherapy or molecularly targeted drugs.  A long-term goal is to translate these viruses and combination strategies to brain tumor patients.