Aplastic anemia encompasses a heterogeneous group of diseases with distinct pathophysiologies and a common clinical endpoint of marrow failure. Patients with severe aplastic anemia can be treated with immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Over the last 30 years, advances in both treatment modalities have significantly improved the prognosis for this disease; yet this evolution complicates the central therapeutic question in aplastic anemia: which patients should receive IST and which ones should receive HSCT as front-line therapy? In this review, we describe the major improvements that have occurred in transplantation for aplastic anemia in the last 3 decades. We then outline a framework for deciding which patients should be considered for upfront transplantation.