Chromosome territories (CTs) are a fundamental feature of nuclear architecture. This article reviews the historical development and experimental evidence supporting the concept of CTs in eukaryotic cells, discusses current knowledge of CT arrangements, their dynamics during the cell cycle and postmitotic differentiation, and highlights open questions and new experimental strategies. It also explores the relationship between CT organization and epigenomic functions. The concept of CTs was first proposed by Carl Rabl in the late 19th century and later formalized by Theodor Boveri, who introduced the term "chromosome territory." Boveri's observations of blastomeres in the nematode Ascaris suggested that chromosomes maintain their individuality during interphase and occupy distinct nuclear regions. Despite initial skepticism, experimental evidence from the 1970s and 1980s, including laser-UV-microbeam experiments and in situ hybridization, provided compelling support for the existence of CTs. CTs are nonrandomly arranged and exhibit distinct spatial organization. Higher-order chromatin arrangements may reflect geometrical constraints or functional advantages. Nonrandom proximity patterns between CTs and chromosomal subregions are of interest in nuclear architecture research. Techniques such as 3D fluorescence in situ hybridization (FISH) have been used to visualize CTs and their substructures, revealing gene density-related radial arrangements. CT arrangements are stable during interphase but can change during mitosis and postmitotic differentiation. For example, in mammalian retinal rod cells, heterochromatin moves to the nuclear interior during postmitotic terminal differentiation, while euchromatin shifts to the nuclear periphery. This reorganization is crucial for adapting to low-light vision. CTs are dynamic and can change during cellular differentiation. In murine cerebellar Purkinje neurons, CT repositioning occurs as centromere positions stabilize. Specific gene loci on the same or different CTs can exhibit long-range spatial interactions, such as "gene kissing," which may be involved in gene regulation. The CT-interchromatin compartment (CT-IC) model suggests that nuclei are composed of CTs and an interchromatin compartment (IC), with the IC containing splicing speckles and other nuclear bodies. The IC is a DNA-free space that may play a role in transcription and RNA processing. However, other models, such as the interchromatin network (ICN) model, propose a more uniform chromatin arrangement without distinct compartments. The article concludes with open questions about CT organization and the need for further experimental strategies to address them. Current research emphasizes the importance of understanding the functional implications of CT arrangements in epigenomics and nuclear architecture.Chromosome territories (CTs) are a fundamental feature of nuclear architecture. This article reviews the historical development and experimental evidence supporting the concept of CTs in eukaryotic cells, discusses current knowledge of CT arrangements, their dynamics during the cell cycle and postmitotic differentiation, and highlights open questions and new experimental strategies. It also explores the relationship between CT organization and epigenomic functions. The concept of CTs was first proposed by Carl Rabl in the late 19th century and later formalized by Theodor Boveri, who introduced the term "chromosome territory." Boveri's observations of blastomeres in the nematode Ascaris suggested that chromosomes maintain their individuality during interphase and occupy distinct nuclear regions. Despite initial skepticism, experimental evidence from the 1970s and 1980s, including laser-UV-microbeam experiments and in situ hybridization, provided compelling support for the existence of CTs. CTs are nonrandomly arranged and exhibit distinct spatial organization. Higher-order chromatin arrangements may reflect geometrical constraints or functional advantages. Nonrandom proximity patterns between CTs and chromosomal subregions are of interest in nuclear architecture research. Techniques such as 3D fluorescence in situ hybridization (FISH) have been used to visualize CTs and their substructures, revealing gene density-related radial arrangements. CT arrangements are stable during interphase but can change during mitosis and postmitotic differentiation. For example, in mammalian retinal rod cells, heterochromatin moves to the nuclear interior during postmitotic terminal differentiation, while euchromatin shifts to the nuclear periphery. This reorganization is crucial for adapting to low-light vision. CTs are dynamic and can change during cellular differentiation. In murine cerebellar Purkinje neurons, CT repositioning occurs as centromere positions stabilize. Specific gene loci on the same or different CTs can exhibit long-range spatial interactions, such as "gene kissing," which may be involved in gene regulation. The CT-interchromatin compartment (CT-IC) model suggests that nuclei are composed of CTs and an interchromatin compartment (IC), with the IC containing splicing speckles and other nuclear bodies. The IC is a DNA-free space that may play a role in transcription and RNA processing. However, other models, such as the interchromatin network (ICN) model, propose a more uniform chromatin arrangement without distinct compartments. The article concludes with open questions about CT organization and the need for further experimental strategies to address them. Current research emphasizes the importance of understanding the functional implications of CT arrangements in epigenomics and nuclear architecture.