Telomerase expression and telomere maintenance are critical for long-term cell proliferation and survival, and they play important roles in development, aging, and cancer. Cumulating evidence has indicated that regula-tion of the rate-limiting subunit of human telomerase reverse transcriptase gene (hTERT) is a complex process in normal cells and many cancer cells. In addition to a number of transcriptional activators and repressors, the chromatin environment and epigenetic status of the endogenous hTERT locus are also pivotal for its regula-tion in normal human somatic cells and in tumorigenesis.