The telomerase deficient mouse has been invaluable in providing insights into basic questions pertaining to consequences of telomere dysfunction during aging and cancer in the context of the mammalian organism. Studies using this mouse model have demonstrated that cellular responses to telomere dysfunction are fundamentally conserved in both humans and mice, and that the tight regulation of telomere length and telomerase activity in somatic cells may be important in mediating the balance between aging and cancer. Here, I discuss the use of the telomerase null mouse for understanding the contrasting roles of telomeres and telomerase in organismal aging and cancer.