Abstract: In pediatric medical settings, the evaluation of health-related quality of life (HRQOL) has become increasingly standard in treatment planning and outcome. Few studies have examined the clinical utility of HRQOL measurement, and no previous study has done so in pediatric rheumatology. This study explored longitudinal assessment of HRQOL using the Pediatric Quality of Life Inventory™ (PedsQL™) 4.0 Generic Core Scales (GCS) and Rheumatology Module (RM) in 255 children with a rheumatic diagnosis. The relationship of HRQOL to biological and clinical variables (medication use, laboratory tests, and physician global assessment) was also explored. Analysis of variance, correlation, and multiple regression were used to analyze these relationships. After controlling for demographic factors, for both child self-report and parent proxy report, children with fibromyalgia syndrome (FMS) reported significantly lower HRQOL than all other diagnostic groups on the GCS and some RM subscales. For the total sample, there was an overall significant improvement in HRQOL over time, primarily for child self-report, with the greatest differences in physical functioning and pain subscales. Although each group evidenced improvement in HRQOL over time, these findings were not significant after adjusting for the number of comparisons. Physician ratings of the utility of the PedsQL™ indicate that in cases where the PedsQL™ was rated as useful during patient evaluation, both the physical and psychosocial domains were equally helpful. For the total sample, the physician global assessment correlated significantly with the child's HRQOL scores; correlations were not significant for many diagnosis groups. Children taking medication reported significantly lower HRQOL than children without medication, however, there were no significant differences in HRQOL by medication type. Similarly, there were no significant differences in HRQOL for laboratory measures of disease severity for any diagnostic group except systemic lupus erythematosus. Findings suggest that children with rheumatic conditions report low HRQOL when compared to healthy children scores, although scores improve with treatment. Additionally, results emphasize a need for interventions aimed at improving HRQOL specifically for children with fibromyalgia. Finally, while this study found some utility of HRQOL assessment in clinical settings, many questions remain unanswered. Recommendations for future research are discussed.