The genome is carried by the complete linear sequence of DNA nucleotides packaged into all the chromosomes. During interphase, the chromosomes are extended and much of their chromatin exist as long threads while also maintaining specific three-dimensional architectures in the nuclear space. These interphase chromosomes are organized into multiscale three-dimensional structures, including chromosome territories, A/B compartments, topologically associating domains, and chromatin loops, that extend over a wide range of genomic distances, providing connections, for instance, between enhancers and promoters. This hierarchically organized genomic architecture is crucial for the regulation of gene transcription, which in turn is essential for the development and maintenance of various biological processes. This article reviews various aspects of spatial genome organization and their functions in gene expression and neural development. Furthermore, dysregulation of spatial genome organization in disease states, and the growing interest in new technologies to manipulate chromatin architecture are also discussed.