Telomerase activation is observed in almost 90% of human cancers but not in normal tissues of somatic origin and thus is a critical step for multistep carcinogenesis. A more thorough understanding of telomerase regulation may provide not only a molecular basis of cancer progression but also as a way to manipulate telomerase activity as a potential therapeutic modality. Recent progress in studies on telomerase regulation has shown that telomerase activation is achieved at various steps, including transcriptional and post-transcriptional levels of the telomerase reverse transcriptase (hTERT) gene. Although a number of potentially important mechanisms of telomerase activation have been proposed, none of the current models can fully explain tumor-specific activation of telomerase, suggesting a need for further extensive analysis. This review includes a summary of recent works on telomerase regulation and a discussion of how we can overcome this situation.