Following the importances of telomere and telomerase in senescence and tumor were recognized, the pathway of telomerase activation is becoming the focus of this area. By now, MYC was found to play key role in telomerase activation. It could activate telomerase directly by binding to E-box in promoter region of TERT gene. At the same time, MYC might mediate other molecules to activate telomerase, such as HPV-E6 and estrogen. Estrogen could activate telomerase directly by forming estrogen/estrogen receptor complex binding to imperfect palindromic degenerate estrogen-responding element in promoter region of TERT gene. APC, p53 and protein phosphorylation might also involve in telomerase activation.