OBJECTIVES: Hemophilia A is a rare but serious bleeding disorder caused by a blood clotting factor VIII (FVIII) deficiency. To examine the impact of hemophilia A and replacement FVIII therapies from a humanistic and economic perspective, a targeted literature review was conducted. METHODS: Searches were conducted in MEDLINE® and the National Health Service Economic Evaluation Database, using disease, patient-reported outcome and economic-related key words, limited to English articles published from January 2000-January 2010 (inclusive). From 653 abstracts retrieved, 34 full-text articles were selected for detailed consideration. RESULTS: Findings revealed increased mortality rates and decreased life expectancy among people with hemophilia A, compared with the general population. This is largely attributed to the transmission of blood-borne viruses (e.g. HIV and Hepatitis-C) due to use of plasma-derived FVIII (pdFVIII) concentrates. Improvements in viral attenuation processes plus donor screening practices for pdFVIII products have reduced the risks of viral transmission, but risk from non-enveloped viruses and other unknown pathogens still exists. Newly developed recombinant FVIII therapies minimize these risks; however, such therapies are not currently widely available globally. All available FVIII therapies use demanding regimens requiring regular time-consuming injections, which can be detrimental to patients’ health-related quality of life and limit adherence. Non-adherence is associated with diminished product efficacy, poorer health outcomes and increasing economic expenditure. Treating hemophilia A is costly, primarily due to the high acquisition cost of replacement FVIII products. However, indirect costs (e.g. patient disability) also contribute to economic burden. Prophylactic treatment, while initially more expensive than on-demand treatment, is associated with greater clinical efficacy and improved long-term outcomes, which may lead to cost savings over a patient’s lifetime. CONCLUSIONS: Hemophilia A is associated with considerable humanistic and economic burden. Substantial unmet needs remain among hemophilia A patients with regard to the safety, convenience and global access to FVIII therapy.