Telomere maintenance and end protection are essential for the survival and proliferation of eukaryotic cells, leading to the prediction that components of this system would be highly conserved. In practice, however, evidence for homology among these factors has been elusive, and, in the case of the known end-protection proteins, evolutionary relationships have been postulated largely on the basis of protein structural and functional similarity alone. Here we report support from sequence profile analyses for a significant and specific evolutionary relationship among OB-fold telomeric end-protection factors.