Patient-reported outcomes such as Quality of Life often play an important part in the efficacy assessment of drug treatment. Although instruments that measure quality of life can detect the positive effects of treatments on health status, they may not measure the effect of negative treatment-related symptoms. Patients often fail to spontaneously report common or clinically mild drug-related symptoms, even though the same symptoms can result in the stopping or skipping of prescribed doses. Therefore, as with quality of life assessments, the perception of patients on possible side effects of treatments is best captured by the use of self-report questionnaires. There are substantial challenges with creating well-validated, relevant questionnaires that capture the full range of patient-reported symptoms and signs. A review of 13 existing instruments showed that many patient-rated side effect questionnaires had been developed, often to a high standard, using well-established psychometric methods. However, there were some inconsistencies in the methods used by the questionnaire developers, indicating the need for standardisation when creating new, or adapting previous, instruments. Even with their current deficits, it is important that patient-reported side effect questionnaires be used more in drug development, health outcomes research and resource allocation; all with the ultimate aim of improving quality of patient care. Copyright © 2008 John Wiley & Sons, Ltd.