Neurological disorders such as traumatic brain injuries or stroke result in neuronal loss and disruption of the brain parenchyma. Current treatment strategies are limited in that they can only mitigate the degeneration process or alleviate the symptoms but do not reverse the condition. In contrast, regenerative cell-based therapies offer long-term hope for many patients. Bioactive scaffolds are likely to reinforce the success of cell replacement therapies by providing a microenvironment that facilitates the survival, proliferation, differentiation, and connectivity of transplanted and/or endogenous cells. This Review outlines various biomaterials (including hydrogels, self-assembling peptides, and electrospun nanofibres) that have been investigated for the repair of brain tissue, and discusses strategies for the immobilization of biomolecules. An overview of the potential clinical applications of such scaffolds in neurodegenerative diseases is also provided.