The decision to pursue hematopoietic stem cell transplantation or immunosuppression as first therapy in severe aplastic anemia is currently based on age and availability of a histocompatible donor. The ability to predict hematologic response, relapse and clonal evolution could improve treatment allocation. In the past 15 years, telomeres have been implicated in clinical diseases such as aplastic anemia, pulmonary fibrosis, cirrhosis and cancer development. The clinical relevance of varying telomere lengths (TL) and/or mutations in genes of the telomerase complex (TERC, TERT) is evolving in aplastic anemia. A large retrospective analysis suggests that baseline TL associate with late events of hematologic relapse and clonal evolution in aplastic anemia patients treated initially with anti-thymocyte globulin-based therapy. Further laboratory experiments propose possible mechanistic insight into genomic instability of bone marrow cells derived from patients with critically short telomeres and/or mutation in telomerase genes. The possibility of modulating telomere attrition rate with sex hormones could positively affect clonal evolution rates in humans. This review will summarize studies in marrow failure that explore the association between telomeres and aplastic anemia outcomes.