Chromosome ends, or telomeres, are formed by a special chromatin structure that protects them from recombination and degradation, thus preventing end-to-end chromosome fusions and other chromosomal aberrations. The functionality of telomeres, and that of the cellular activity that synthesizes them, telomerase, has been shown to impact on both cancer and aging, as well as on the organismal sensitivity to ionizing radiation. This review focuses on the analysis of different mouse models for proteins that are important for telomere function, which have highlighted the importance of telomeres and telomerase for cancer and aging.