The ends of linear eukaryotic chromosomes are transcribed into different species of non-coding transcripts (the telomeric transcriptome), including TERRA (telomeric repeat-containing RNA) molecules; however, the functions associated with the telomeric transcriptome remain elusive. Experimental evidence accumulated during the past few years indicates that the transcriptional activity of telomeres is changed in cells in which the integrity of the telomeres or the heterochromatic state of chromosome ends is altered. On the contrary transcription of a telomere appears not to be influenced by its length. In this paper we briefly review the current state of knowledge on the composition, biogenesis, and regulation of the telomeric transcriptome from yeasts to humans. We also suggest a model in which TERRA is part of the DNA damage response triggered by dysfunctional telomeres and discuss the potential involvement of telomere transcription in the development of human pathologies.