Adenoviruses have been critical in the development of the molecular approaches to brain tumors. They have been engineered to function as vectors for delivering therapeutic genes in gene therapy strategies, and as direct cytotoxic agents in oncolytic viral therapies. This review outlines the uses of adenoviruses in brain tumor therapy by examining clinical trials of adenovirus-mediated p53 gene therapy and by reviewing the application of two conditionally replicative adenoviruses (CRAds) ONYX-015 and Delta 24 in brain tumors. The potential clinical use of CRAds that deliver trangenes, particularly p53, is also discussed.