Telomeres are capping structures at the ends of eukaryotic chromosomes, which consist of repetitive DNA bound to an array of specialized proteins. Telomeres are part of the constitutive heterochromatin and are subjected to epigenetic modifications. The function of telomeres is to prevent chromosome ends from being detected as damaged DNA. Both the length of telomere repeats and the integrity of the telomere-binding proteins are important for telomere protection. Telomere length is regulated by telomerase, by the telomere-binding proteins, as well as by activities that modify the state of the chromatin. Various mouse models with altered levels of telomerase activity, or mutant for different telomere-binding proteins, have been recently generated. Here, I will discuss how these different mouse models have contributed to our understanding on the role of telomeres and telomerase in cancer and aging.