Advances in our understanding of stem cell interactions with their environment are leading to the development of new materials-based approaches to control stem cell behavior toward cellular culture and tissue regeneration applications. Materials can provide cues based on chemistry, mechanics, structure, and molecule delivery that control stem cell fate decisions and matrix formation. These approaches are helping to advance clinical translation of a range of stem cell types through better expansion techniques and scaffolding for use in tissue engineering approaches for the regeneration of many tissues. With this in mind, this progress report covers basic concepts and recent advances in the use of materials for manipulating stem cells.