To ensure sister chromatids to be equally transmitted to daughter cells, it is imperative that physical association of sister chromatids is maintained during S, G2, and early mitosis until the onset of anaphase. Cohesion of sister chromatids in eukaryotes is largely achieved by the cohesin complex. In vertebrates, cohesin molecules are dissociated from chromosome arms but not from centromeres during prophase by the so-called prophase pathway. Although it remains unclear what is the molecular basis by which centromeric cohesin is retained, a flurry of recent studies have shed light on a family of proteins named Shugoshin (Sgo) that are evolutionarily conserved across eukaryotes. Sgo1 functions as a protector of centromeric cohesin during meiosis in yeast and during mitosis in high eukaryotes. Suppression of Sgo1 function results in premature separation of sister chromatids in both meiosis and mitosis. The discovery of members of the Sgo family may help to explain how centromeric cohesin is protected from dissociation from DNA until the onset of anaphase. Given the importance of chromosome cohesion in the maintenance of genomic stability, further characterization of Sgo1 and related molecules may also open up new avenues of research for developing new strategies for cancer intervention.