Aplastic anemia may be the result of the immune attack against hematopoietic stem and progenitor cells or the impairment of appropriate hematopoietic stem cell function due to inherited genetic defects. Although bone marrow transplantation is the preferential therapy for severe cases, the majority of patients lack a suitable sibling donor. The thrombopoietin receptor agonist eltrombopag has been recently added to immunosuppressive therapy, reaching high response rates and overall survival, rivaling matched-donor transplant results. Additionally, genetic defects in telomere-maintenance genes appear to be the most prevalence etiology of inherited aplastic anemia. Sex hormones may recover hematopoiesis in these cases. The occurrence of somatic genetic mutations in immune and inherited aplastic anemia may help to understand the complex dynamics of hematopoietic stem cells in vivo.