INTRODUCTION: Side effects include drug-induced symptoms which are predominantly communicated by patient self-report. This year, the FDA produced draft recommendations for the validation of patient-reported outcomes, for use in medical product development studies. The growing interest in side effects in medical research and the regulatory environment, presents an urgent need for properly developed patient-reported outcome measures of drug side effects. These measures must be valid, reliable and reproducible. METHODS: To assess the psychometric properties of patient-reported side effect symptom scales, and to describe and evaluate the methodologies used to create them. RESULTS: Fifteen existing scales were identified and reviewed. There was wide variation in the extent to which the psychometric properties of the instruments had been reported or tested. There were disagreements amongst scale developers concerning the appropriateness of use of certain reliability tests which are usually routinely undertaken during questionnaire development. The responsiveness testing of side effect scales may be problematic to carry out and testing was limited amongst reviewed scales. Since any symptom of a drug intervention may be associated with everyday health problems, the disease being treated, the drug treatment or a combination of these causes, measuring drug-related side effects is complicated. This complexity impacts upon all aspects of the psychometric testing of patient–reported scales, creating unique challenges for their developers, who must create tools which appropriately discriminate between side effects and symptoms. CONCLUSION: The potential usefulness of patient-reported side effect scales is broad: from research outcome to clinical monitoring. However, a consensus must be reached on suitable methods for the development of such scales. The complexity of side effect measurement may necessitate the introduction of new approaches for the assessment of the reliability and responsiveness of these scales.