Human telomerase reverse transcriptase (hTERT) has been identified as a major protein involved in aberrant cell proliferation, immortalization, metastasis and stemness maintenance in a majority of tumors, yet it has little or no expression in normal somatic cells. During the past few years, the development of hTERT-based therapies such as immunotherapy, suicide gene therapy and small-molecule interfering therapy have become critical and specific for eradicating all types of cancer. Here, current knowledge regarding hTERT and its involvement in various cancers and its role as a target of cancer therapies are reviewed. Additionally, hurdles to new cancer therapy development and new therapeutic opportunities are described, along with areas that require further investigation.