There is now abundant experimental evidence in multiple human cell types in culture for the causal relationships between telomere loss and replicative senescence on one hand, and telomerase activation and cellular immortalization on the other. These relationships are supported by correlative data in human aging, chronic diseases, cancer, experiments in telomerase knock-out mice, and human genetic conditions of telomerase insufficiency. However, final, definitive data that telomere biology plays a causal role in normal human aging and age-related diseases, including cancer, will only come with specific therapeutic intervention. We have worked on development of telomerase vaccines, telomerase inhibitors, and telomerase promoter-driven cell killing in oncology, and now have a therapeutic vaccine in the clinic, and a telomerase antagonist in late preclinical studies. We are also working on telomerase activation for a broad range of degenerative diseases in which replicative senescence or telomere dysfunction may play a role. Unfortunately, the strong link between telomerase and cancer has led some to confuse telomerase activation with cancer, and others to overstate the cancer risk of telomerase activation therapies for degenerative diseases. This presentation will provide an update on the status of telomerase-based cancer therapeutics, and review the data that suggest transient telomerase activation may be a safe and effective approach to regenerative medicine while reducing, rather than increasing, the frequency of age-related tumorigenesis.