The efficacy of anti-thymocyte globulin (ATG) as prophylaxis for graft-versus-host disease (GVHD) has been investigated by many clinical studies over the past decade, including some randomized controlled trials. Intriguingly, although ATG is commonly used as prophylaxis for GVHD, there is still controversy about the optimal dose of ATG for prophylaxis of GVHD after allogeneic hematopoietic cell transplantation (allo-HCT). Indeed, the dose and formulation of ATG, as well as the degree of clinical benefit, has varied among studies, which makes it difficult to fully determine the clinical benefit of ATG. The aim of this review is to summarize the information regarding the optimal ATG dose of each formulation according to stem cell source, and to discuss how best to determine the personalized optimal dose of ATG in each allo-HCT recipient.