Patient-generated outcomes attempt to capture the individualistic nature of quality of life. Although this is an attractive concept, a critical review of these instruments is needed to assess their applicability in a clinical trial setting. OBJECTIVE: To provide a critical review of four patient-generated quality of life instruments: Patient-Generated Index (PGI), Schedule for the Evaluation of Individual Quality of Life (SEIQoL), Repertory Grid, and Asthma Quality of Life Questionnaire (AQLQ). METHODS: We conducted a systematic literature review of available computerized databases, the Quality of Life Research Journal and consulted experts in the field. We abstracted data from the studies and constructed a matrix comparing the four instruments based on their psychometric properties and current use in quality of life research. RESULTS: The PGI and SEIQoL have been shown to be reliable and valid in several different patient populations and disease states; however, neither have been used in a clinical trial. The SEIQoL-DW, in addition, has been shown to be practical and acceptable to patients. The Repertory Grid has been shown to be reliable, valid and practical, but has only been used in one observational study. The AQLQ is a disease-specific instrument that is only partially patient-generated. It has not only shown to be reliable, valid and practical, but has also been used in clinical trials as a sole measure of quality of life. CONCLUSION: Patient-generated outcomes may not be generally useful in a clinical trial setting. However, hybrid instruments, such as the AQLQ, may be applicable in a clinical trial setting. The primary role of patient-generated outcome measures is as an adjunct measure or to guide individual patient treatment decisions.