Telomerase is known to be activated in almost all cancer cells and is quiescent in almost all normal cells. Therefore, it follows that therapeutic strategies directed against cancer would include the targeting of telomerase, as well as the use of telomerase. Several approaches have been used both in vitro and in vivo and include the following: 1) antisense; 2) immunotherapy directed against hTERT; and 3) the use of telomerase promoter to direct cytotoxic therapy. Herein we review these approaches and discuss their potential applicability against thyroid cancer.