Evolving from a normal cell to a cancer cell requires overcoming or evading safeguard mechanisms that maintain cellular integrity. One such mechanism is the limitation of telomere shortening, a crucial factor in regulating cell division and ensuring genomic stability. Telomeres are protective caps at chromosome ends that prevent progressive DNA loss during replication. As cells divide, telomeres shorten, and when they reach a critical length, cells enter senescence or undergo apoptosis. Cancer cells must circumvent these limitations to achieve replicative immortality. This chapter explores telomere maintenance mechanisms (TMMs) that enable cancer cells to maintain telomere viability, including telomerase reactivation and the alternative lengthening of telomeres (ALT) pathway. Understanding TMMs is crucial as it provides new opportunities for diagnostic and prognostic biomarkers and potential therapeutic targets.