The continuance of life through cell division requires high fidelity DNA replication and chromosome segregation. During DNA replication, each parental chromosome is duplicated exactly and one time only. At the same time, the resulting chromosomes (called sister chromatids) become tightly paired along their length. This S-phase pairing, or cohesion, identifies chromatids as sisters over time. During mitosis in most eukaryotes, sister chromatids bi-orient to the mitotic spindle. After each chromosome pair is properly oriented, the cohesion established during S phase is inactivated in a tightly regulated fashion, allowing sister chromatids to segregate away from each other. Recent findings of cohesin structure and enzymology provide new insights into cohesion, while many critical facets of cohesion (how cohesins tether together sister chromatids and how those tethers are established) remain actively debated.