Cancer stem cells (CSCs), i.e. cancer cells that can self-renew, constitute only a minority of the cells of a tumour, but, because of their ability to initiate and repopulate tumours, failure to control CSCs can potentially lead to tumour re-growth, even though the bulk tumour may have been treated successfully. Nanomedicines improve spatio-temporal control over drug kinetics and distribution, thus opening the prospect of safer and more specific therapies to address the challenges posed by CSCs. In particular, these systems have the potential to facilitate CSC-aware therapy by overcoming resistance to conventional cytotoxic drugs and by targeting novel therapies to the tumour and CSC-marker positive cells. This review examines the implications of the CSC paradigm specifically for the development of nanomedicines, i.e. therapies based on macromolecules or supramolecular aggregates.