Environment-epigenome interactions are emerging as contributors to disease risk and health outcomes. In fact, organisms outside of the laboratory are constantly exposed to environmental changes that can influence chromatin regulation at multiple levels, potentially impacting on genome function. In this review, we will summarize recent findings on how major external cues impact on 3D chromatin organization in different experimental systems. We will describe environment-induced 3D genome alterations ranging from chromatin accessibility to the spatial distribution of the genome and discuss their role in regulating gene expression.