The field of experimental dermatology research has dramatically benefited from the insights yielded by in vivo studies on animal models. Indeed, much of our understanding of the mechanisms that regulate embryonic skin development, adult skin homeostasis and physiological skin responses to stress, such as wound healing, has been educated by studies conducted in animal models, including mutant mice. These works become commonly published on the pages of Experimental Dermatology and, in fact, represent one of the core interests of the journal. Highlighting in vivo mouse model studies are recent works on hair follicle development and growth 1-5 and wound healing. 6-8 Further, studies in animal models often help to elucidate aspects of disease pathogenesis, and mouse models are used to investigate mechanisms of human skin conditions such as atopic dermatitis, 9-13 contact dermatitis, 14-16 psoriasis, 17,18 rosacea 19 and squamous cell carcinoma 20 to name a few. On the other hand, not all human skin diseases or aspects of human skin physiology can be reliably modelled in rodents. This is not surprising, considering that humans and rodents are separated by an estimated 96 million years of evolution. 21 Addressing this fact, many studies are being conducted on patient-derived primary skin cells, including human keratinocytes, 22-25 melanocytes, 26-30 fibroblasts 31-34 and cell co-cultures. 35-37 However, typical in vitro culture conditions fail to replicate and, in fact, do not come close to imitating the biomechanical and biochemical complexity of the microenvironment in which cells exist and to which they respond to in native tissues. Further, ingredients in commonly used cell culture media and the two-dimensional constraints of growth on plastic result in cells being exposed to a lot of artificial cues, to which they adapt but also prominently alter their gene expression profile and functional activities in the process. Therefore, behaviours displayed by skin cells in twodimensional cultures need to be comprehensively validated under more native-like conditions in order to be deemed biologically and physiologically relevant. Helping to bridge the gap, threedimensional (3D) organotypic cultures and organ culture techniques have long been a highly instructive tool for investigating complex, tissue-level behaviours by skin cells.