Although the search for pharmacologic inhibitors of telomerase activity represents a promising approach for telomerase-based anti-cancer therapy, the immunological properties of the telomerase reverse transcriptase hTERT suggest that the enzyme is also an attractive target for novel immunotherapies against cancer. Data from both human and murine systems demonstrate that cytotoxic T-lymphocytes (CTL) can recognize peptides derived from TERT and kill TERT-positive tumor cells of multiple histologies. Given the vast overexpression of hTERT in human tumors and its low-level expression in rare normal tissues, clinical trials have begun that test the credentials of hTERT as a broadly applicable target for immunotherapy of cancer.