This chapter intends to update the quality of life issue in hemophilia. A short overview of the quality of life construct and its link with health and well-being will be addressed. The importance of the evaluation of the health-related quality of life (HRQoL) as a health outcome, the objectives of HRQoL research, the types of measurement and instrument characteristics, the criteria for choosing a patient-reported outcome (PRO) measure within several, the disease specific health-related quality-of-life instruments available for hemophilia, and the evidence of hemophilia clinical indicators impacting health-related quality-of-life measured by PRO will be addressed as well. Evidence described by studies assessing HRQoL damage in hemophilia patients with inhibitors will be also mentioned.