Despite their much-heralded clinical potential, therapeutic cancer vaccines have thus far failed to achieve the necessary clinical benchmarks to allow their regulatory approval. In contrast, vaccination against infectious pathogens represents one of the biggest achievements of modern medicine, and in certain cases such as vaccines against the human papilloma virus or hepatitis B virus, vaccination may impact the development of cancer. To the extent that these two approaches differ as immunotherapy vs. immunoprevention, the challenge is to rethink the types of non-viral antigens that are currently being targeted in cancer vaccines. Immunological analysis suggests that the telomerase reverse transcriptase hTERT is a widely applicable target recognized by T lymphocytes and a prototype for a novel class of universal tumor antigens. Findings from initial clinical trials demonstrate that hTERT-specific immune responses can be safely induced in cancer patients. If the amplitude and duration of cellular immunity against hTERT can be optimized without toxicity in humans, then an opportunity exists to test hTERT vaccination as a way to reduce the risk of cancer recurrence in patients or even the risk of developing cancer in otherwise healthy individuals.