Existing brain tumor therapies, such as radiation and chemotherapy, are associated with harmful effects on the central nervous system (CNS). Neurologic complications include both structural and functional brain changes, such as progressive brain atrophy, white matter injury, and cognitive impairment. Long-term survivors are particularly affected by such treatment related complications. Importantly, there are no available therapies to prevent brain injury and strategies to limit neurotoxicity or enhance brain repair are urgently needed. This presentation will review the current understanding and cell-biological mechanisms of cancer therapy associated neurologic complications. Novel concepts of brain plasticity and evolving brain repair strategies will be discussed.