Telomerase reverse transcriptase (TERT) is expressed constitutively in tumour cells throughout the evolution of many cancers; therefore, this potential tumour self-antigen has been an important target for anticancer vaccines over the past 10 years, but only modest benefits from this approach have been observed in clinical trials. In this Perspectives, Maurizio Zanetti reviews these studies, and highlights advances in our knowledge that warrant further development and refinement of TERT immunotherapy.