Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding essentially unlimited numbers of daughter cells that can maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells can only preserve their unique functions if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer functional de novo stem cells niches outside of the body and (ii) to target stem cell niches in vivo. Such ‘artificial niches’ constitute powerful tools for elucidating stem cell regulatory mechanisms with the potential to directly impact the development of novel therapeutic strategies for tissue regeneration.