Poly(N-isopropylacrylamide) (pNIPAm) microgel-based materials can be fabricated that self-fold into three-dimensional structures in response to changes in the environmental humidity. The materials are composed of a semi-rigid polymer substrate coated with a thin layer of Au; the Au layer is subsequently coated with a pNIPAm-based microgel layer and finally covered with a solution of polydiallyldimethylammonium chloride (pDADMAC). The pDADMAC layer contracts upon drying causing the material to deform (typically bending); this deformation is completely reversible over many cycles as the environmental humidity is systematically varied. Here, by varying the size and aspect ratio of the polymer substrate, it is possible to develop a set of empirical rules that can be applied to predict the material's self-folding behavior. From these rules, materials that self-fold from two-dimensional, flat objects into discrete three-dimensional structures, which are fully capable of unfolding and folding multiple times in response to humidity, are designed.