One important challenge for cell biology in the post-genomic era is to understand how genomes are organized within the nuclear space and how this organization contributes to genome stability, gene expression and DNA metabolism. In yeasts, chromosomes are anchored to the nuclear envelope via specific DNA loci such as centromeres, telomeres and TFIIIC binding sites. This remarkable topological organization requires the presence of distinct DNA sequences and chromatin domains and relies on a large number of proteins that mediate chromatin interactions with the nuclear envelope. Therefore, the nuclear envelope serves as a dynamic scaffold to anchor and organize distinct chromosomal domains, thus generating a higher-order nuclear architecture. This review summarizes the current knowledge on the spatial organization of the fission yeast genome and its implications for nuclear function.