Gene expression patterns in complex multicellular organisms are regulated by enhancers, which communicate with their target gene promoters in three-dimensional (3D) chromatin structures. Despite advances in our understanding of the mechanisms that organize mammalian genomes into compartments and topologically associating domains (TADs), it is not well understood how specific interactions between enhancers and promoters are controlled in this 3D context. In this review, we give an overview of recent evidence that shows that a process of loop extrusion plays an important role in the regulation of enhancer–promoter communication and discuss recent insights into the molecular mechanism by which loop extrusion contributes to enhancer-mediated gene activation.