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Health-related quality of life is an individual’s perception of his or her health and it is an important outcome measure for clinical research in orthopaedics. For clinical outcomes research related to the knee, measures of health-related quality of life should consider disability imposed by impairment of the knee. Health-related quality of life is measured by assembling questions to represent the construct of health-related quality of life. Validation of health-related quality of life requires evidence to support the interpretation and usefulness of the resulting score. The purpose of the current paper was to provide readers with a framework for identifying and selecting relevant clinical outcome measures that should be considered when designing clinical research related to the knee. The need to include reliable, valid, and responsive measures of health-related quality of life in clinical outcomes research related to the knee was discussed and the process for developing such measures was shown by describing the process used to develop the International Knee Documentation Committee Subjective Knee Form.