The mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved regulator of longevity that plays a central role linking environmental cues to aging biology. The mTOR inhibitor rapamycin is currently the most effective and reproducible pharmacological approach to extending lifespan in animals. Several groups have independently shown that short-term treatment with rapamycin in mice can prevent age-related decline or rejuvenate functional measures of health in various organs and tissues including brain, heart, kidney, muscle, oral cavity, immune system, and ovary. Multiple clinical trials have been, or will soon be, initiated with the goal to determine whether rapamycin can positively impact age-related endpoints in humans and companion dogs. Several hundred “biohackers” are proactively using rapamycin off-label in hopes that it will increase healthspan and lifespan and a growing number of medical practitioners are prescribing rapamycin for such “off-label” use.