Acute leukemias are aggressive hematological cancers with high mortality, curable only through intensive chemotherapy with or without hematopoietic stem cell transplantation. Therefore, patients with acute leukemia face a considerable impairment of quality of life (QOL), both short term and long term. However, most physician’s effort is directed to prolonging patients’ lives. Similarly, the majority of studies focus on survival end-points only and do not take QOL into consideration. There is also no consensus concerning the most appropriate instrument for assessing patient’s QOL; few are adapted for hematological malignancies. Of note, there are acute leukemia-specific health-related QOL issues, like long hospital stays and invasive diagnostic and treatment procedures, which cannot be estimated by generic QOL-assessing instruments. There is great necessity to identify the most appropriate instrument for measuring health-related QOL in acute leukemia patients. Acquiring additional information on the QOL in various treatment settings enables us to select the most optimal treatment approach when discussing options with patients, with the recognition that prioritizing an extension of survival in “good health” holds greater significance than mere survival extension. There is considerable room for improvement in supportive care, especially in situations where a cure is highly unlikely.