Cellular senescence, a persistent form of cell cycle arrest, has been linked to the formation of heterochromatic foci, accompanied by additional concentric epigenetic layers. However, senescence is a highly heterogeneous phenotype, and the formation of these structures is context dependent. Recent developments in the understanding of the high-order chromatin organization have opened new avenues for contextualizing the nuclear and chromatin phenotypes of senescence. Oncogene-induced senescence displays prominent foci and typically exhibits increased chromatin compartmentalization, based on the chromosome conformation assays, as marked by increased transcompaction and segregation of the heterochromatin and euchromatin. However, other types of senescence (e.g., replicative senescence) exhibit comparatively lower levels of compartmentalization. Thus, a more integrative view of the global rearrangement of the chromatin architecture that occurs during senescence is emerging, with potential functional implications for the heterogeneity of the senescence phenotype.