The increasing recognition of the patient perspective and, more specifically, functioning and health, has led to an impressive effort in research to develop concepts and instruments to measure them. Health-Related Quality of Life (HRQOL) and the International Classification of Functioning Disability and Health (ICF) represent two different perspectives from which to look at functioning and health. Therefore, it is expected that both will often be used concurrently in clinical practice, research and health reporting. The objective of our study was to examine the relationship between six HRQOL instruments (the SF-36, the NHP, the QL-I, the WHOQOL-BREF, the WHODASII and the EQ-5D) and the ICF. All six HRQOL instruments were linked to the ICF separately by two trained health professionals according to ten linking rules developed specifically for this purpose. The degree of agreement between health professionals was calculated by means of the kappa statistic. Bootstrapped confidence intervals were calculated. In the 148 items of the 6 instruments a total of 226 concepts were identified and linked to the ICF. The estimated kappa coefficients range between 0.82 and 0.98. The concepts contained in the items of the HRQOL instruments were linked to 91 different ICF categories, 17 categories of the component body functions, 60 categories of the component activities and participation, and 14 categories of the component environmental factors. Twelve concepts could not be linked to the ICF at all. In the component body functions, only emotional functions are covered by all examined instruments. In the component activities and participation, all instruments cover aspects of work, but the half of them scarcely cover aspects of mobility. Only four of the six instruments address environmental factors. The ICF proved highly useful for the comparison of HRQOL instruments. The comparison of selected HRQOL instruments may provide clinicians and researchers with new insights when selecting health-status measures for clinical studies.