Physical activity has long been touted as a means of reducing susceptibility to age-related disease and multiple studies have shown reduced mortality rates in individuals with a lifestyle including regular exercise. A variety of mechanisms for how physical activity reduces age-related diseases have been explored and multiple, redundant explanatory mechanisms are likely to emerge. Evidence has emerged that physical activity may impact directly on telomere biology, one of the primary theories of cellular aging. Telomeres are located at the ends of chromosomes and as cells divide, incomplete DNA replication results in telomere shortening; once shortening reaches a critical threshold, cell senescence results. Investigators hypothesize that part of the favorable influence of physical activity on mortality rates and age-related disease occurs through a direct impact on telomere biology, including delaying rates of telomere shortening. The present review examines key recent findings in this area and explores some of the unanswered questions and future directions for the field.