Iron overload (IOL) is a common condition in patients with hematological malignancies(HMs) undergoing hematopoietic stem cell transplantation (HSCT). Pathophysiologically, IOL results in iron-induced toxicity in HSCT by producing reactive oxygen species (ROS), which leads to detrimental effects on hematopoiesis, clonal evolution, and immunosuppression. IOL, therefore, may have a negative impact on the clinical outcomes of HSCT. For patients at a higher risk of developing IOL before HSCT, it is necessary to monitor red blood cell transfusion units, serum ferritin (SF) levels and MRI image of organs, and initiate iron removal therapy as soon as possible. Iron chelating therapy (ICT) might be safe and efficient in the post-HSCT period. We provide an overview of results from experimental and clinical evidence on the current understanding of IOL in patients with HMs undergoing HSCT, involving the underlying pathophysiological and clinical impact of IOL, as well as the significance of iron reduction therapy.