This chapter describes the health-related quality of life burden of peripheral artery disease. Quality of life has been typically assessed using a combination of generic (e.g. Short Form-36) and disease-specific (e.g. intermittent claudication questionnaire or peripheral artery disease quality of life) instruments or questionnaires. Previous studies show people with peripheral artery disease have substantial reduction in health-related quality of life compared to health controls, including reductions in both physical and mental aspects. People with more severe peripheral artery disease have the poorest quality of life. Treatments for peripheral artery disease, such as exercise programmes and revascularisation, have been reported to improve quality of life but the benefit is frequently not durable. New treatment options are needed to achieve durable improvements in quality of life in people with peripheral artery disease.