Brain tumors generally arise as the culmination of a multistep process that involves a variety of genetic abnormalities. Theoretically, replacement of abnormal genes with normal genes is essential to brain tumor treatment. However, it is very difficult to replace all damaged genes. Currently, most clinical protocols for gene therapy in brain tumors include transfer of a gene which can induce tumor cells to die or which can enhance the environment to generate a systemic immune response against the tumor. The former strategy includes suicide gene therapies, tumor suppressor gene therapy and oncolytic virus therapy. The latter adopts immunogene therapy. In this report, we also focus on other gene therapies, such as therapies to control the cell cycle or apoptosis, and promote antiangiogenesis. Gene therapy is generally accepted to be rather safe in recent years. In fact, the current single-gene therapies for brain tumor are limited and probably restricted to a few tumors. Several agents with different mechanisms of action would be necessary to kill heterogenously mixed tumor cells. Further molecular techniques and basic studies may overcome the malignancy of cancers.