Telomeres are highly conserved structures that cap and protect the ends of linear chromosomes. The telomerase enzyme is present in germline cells as well as in many rapidly dividing tissues and serves to maintain chromosome length and integrity during cell division. Telomerase activity is typically reduced as an organism ages, and this phenomenon has been implicated in the aging process. In this Perspective, we focus on the effects of both gene knockout and gene replacement of telomerase in the heart and discuss the implications of these findings for potential cardiovascular therapeutics.