Telomeric DNA at eukaryotic chromosome ends terminates with single stranded 3′ G-rich overhangs. The overhang is generated by the interplay of several dynamic processes including semiconservative DNA replication, 3′ end elongation by telomerase, C-strand fill-in synthesis and nucleo-lytic processing. The mammalian CST (CTC1-STN1-TEN1) complex is directly involved at several stages of telomere end formation. Elucidation of its structural organization and identification of interaction partners support the notion that mammalian CST is, as its yeast counterpart, a RPA-like complex. CST binding at mammalian telomere 3′ overhangs increases upon their elongation by telomerase. Formation of a trimeric CST complex at telomeric 3′ overhangs leads to telomerase inhibition and at the same time mediates a physical interaction with DNA polymerase-α. Thus CST seems to play critical roles in coordinating telomerase elongation and fill-in synthesis to complete telomere replication.