Evaluating patients with adrenal disease is uniquely challenging as biochemical parameters for assessing disease control or adequacy of hormone replacement are imprecise or lacking. QOL measures are increasingly being used to assess patients with adrenal disease, using a range of generic and disease specific measures. Reduced quality of life has been observed in patients with adrenal disease, even when biochemical cure is possible. We performed a systematic review of studies where QOL measures were used to evaluate adults with adrenal disease. The objectives were to describe how QOL has been defined and measured in relation to patients with adrenal disease, to critically appraise the use of QOL measures in this setting, and discuss the clinical implications of these findings. To our knowledge, this is the first systematic review of QOL in patients with adrenal disease. A total of 114 studies were included in the qualitative synthesis. QOL measures were a primary endpoint in 87%. They were used to evaluate interventions (such as glucocorticoid replacement strategies), assess long-term outcome, explore patient viewpoints, and identifying clinical or biochemical correlates. The majority of studies used quantitative methods, with generic SF-36 was the most frequently used measure. However disease specific tools (AddiQOL, CushingsQOL) are increasingly being used, particularly in therapeutic trials. Impaired QOL is shown across a spectrum of adrenal disorders, especially in Cushings syndrome despite biochemical remission and chronic adrenal insufficiency despite glucocorticoid replacement. As QOL measures are highly subjective and specific to the patient, it must be measured in a standardized way, using robust measurement tools, and clearly reported in order to draw valid conclusions. In addition, potential confounders should be minimized. Overall, reporting quality was suboptimal and QOL was defined in only 5% of studies, the implication being that QOL was defined by its measurement.