The worldwide prevalence of obesity has been steadily rising, reaching alarming levels. Obesity, particularly morbid obesity, carries significant health risks to the lives of affected patients, including physical, psychological, and social co-morbidities. Bariatric surgery provides the only effective and sustainable approach to treat morbid obesity and reverse its adverse effects. The reduction in well-being due to poor health in obesity may have adverse effects on health-related quality of life (HR-QOL). There are numerous studies reporting HR-QOL in bariatric patients; however, there is a paucity of studies examining the psychometric properties of the HR-QOL instruments used. The main aim of this review is to identify the instruments used in assessing HR-QOL in bariatric patients and evaluate their content validity. We believe that this is the first systematic review of its kind to look in depth at various generic- and obesity-specific HR-QOL instruments that were used in bariatric surgery, and to analyze their content validity. A systematic and structured search of Ovid databases (1980-2009) was conducted using terms synonymous with bariatric surgery, combined with terms synonymous with HR-QOL instruments. A total of 112 relevant studies were identified, detailing the use of eight generic, nine obesity-specific, and numerous other condition-specific instruments. A conceptual framework comprising 20 domains pertinent to bariatric surgery and morbid obesity was proposed, against which the identified generic- and obesity-specific instruments were assessed. The results of this assessment showed that neither the generic nor the specific instruments were adequate instruments in terms of content validity. Given the lack of adequate HR-QOL instruments in the rapidly developing field of bariatric surgery, we suggest building a new bariatric-specific instrument informed by the proposed framework, which will then enable clinicians to assess the full impact of morbid obesity and bariatric surgery on HR-QOL.