Mounting evidence suggests that there is an interplay between the three-dimensional (3D) genome structure, nuclear organization, and transcription. Recent studies show that the mammalian genome is highly and hierarchically organized in various levels ranging from A and B compartments to specific enhancer-promoter loops. Aberrations in the 3D genome structure have been implicated in various diseases, including developmental disorders and cancer. However, the role of 3D genome structure in gene regulation remains an open and hotly debated topic as a number of studies suggest a limited effect of chromatin structure alterations on gene expression. Over the last two decades, several research groups have focused on the development of methods to probe the 3D structure of the mammalian genome in an ever-increasing resolution. The original Chromosome Conformation Capture (3C) method which was developed to probe physical chromatin interactions between two genomic loci, was later followed by Circularized Chromosome Conformation Capture (4C), Chromosome Conformation Capture Carbon Copy (5C), and genome-wide 3C variations, such as Hi-C. Hi-C 3.0 improves on the original Hi-C protocol, whereas Micro-C overcomes one of the major limitations of Hi-C, offering nucleosome-level resolution. The recently developed Hi-CO also offers nucleosome-level resolution. HiChIP focuses on chromatin interactions mediated by certain proteins. In addition to these methods, multiple imaging techniques have been developed to study genome architecture. Given that some of the aforementioned techniques are challenging, this collection aims to help the scientific community successfully use them and gain new insights into genome biology.