There is a striking consistency in the total number of heart beats accrued over a lifetime across a range of animal species despite vast differences in size. Moreover, an inverse relationship is observed between heart rate and lifespan, leading to speculation that elevated heart rate could significantly affect longevity. It is the aim of this review to analyze heart rate as a contributing factor in defining the functional lifespan of the transplanted human heart, which may unavoidably determine the longevity of the recipient. Sinus tachycardia occurs as a result of sympathetic/parasympathetic denervation, an unavoidable consequence of transplantation. The effect of elevated heart rate in this cohort has been scarcely reported. We highlight herein multitudinous mechanisms whereby elevated heart rate accelerates the deterioration in cardiac function and arterial elasticity due to injury and stress accumulation. Additionally, we propose a significant role for heart rate in confounding the alloimmune response. Tachycardia exacerbates injurious episodes of myocardial ischemia and significantly increases the production of reactive oxygen species via increased metabolism. These factors promote immune infiltration and activation, contributing to acute and chronic rejection. Further research is required to assess the potential therapeutic benefits of heart rate reduction.