Telomeres undergo attrition with each cell division. Leukocyte telomere length (LTL) and telomerase activity have been extensively investigated in a variety of diseases, such as cardiovascular disease and related metabolic risk factors, neurological disorders, and malignancies. Telomere length may be determined by various factors, including the genetic load and environmental factors. At birth, gender difference in the telomere length is not significant, but telomeres are longer in women than in men. This gender discrepancy is probably caused by the effects of endogenous estrogen exposure or hormone replacement treatment (HRT). Estrogen is known to be antioxidant and may increase telomerase activity; therefore, knowledge about the associate between estrogen and telomere length helps explore therapies targeting the telomere-telomerase system as promising treatment for age-related diseases.