Loss of telomere length homeostasis has been linked to age-related disease especially cancer. In this review, we discuss two major causes of telomere dysfunction that potentially lead to tumorigenesis: replicative aging and environmental assaults. Aging has long been recognized as a source for telomere dysfunction through increasing numbers of cell divisions in the absence of sufficient telomerase activity. However, environmental assaults that cause telomere dysfunction are only beginning to be identified and recognized. Environmental stressors that influence telomere length may be physical or induced by psychological situations like stress. Knowledge of all factors, including genetic and environmental forces, that moderate telomere length will be critical for understanding basic mechanisms of human telomere maintenance during development and aging as well as for disease prevention and treatment strategies.