BACKGROUND: Optimal care of the pediatric chronic kidney disease/end stage renal disease (CKD/ESRD) patient must now incorporate health-related quality of life (HRQOL) assessment and management. METHODS: This study reports the first data on longitudinal change in global (PedsQL(TM)4.0) and disease-specific (PedsQL(TM)3.0 ESRD Module) HRQOL pediatric ESRD patient and proxy ratings over four assessment periods spanning approximately a 2-year period. General linear mixed modeling was used to analyze associations between patient demographics, medical variables, and patient and proxy HRQOL scores. RESULTS: Self-reported and/or proxy data were available for at least two time-points for 53 patients (age 2-18 years; 60 % male), of whom 27 were receiving in-center hemodialysis. CONCLUSIONS: Patient ratings on global health and physical activity, emotional, and social and disease-specific worry and communication domains were higher (i.e., better) than parent-proxy ratings, confirming the importance of obtaining both sources of information. Patients on dialysis longer, particularly females, reported worse emotional functioning; females also reported more physical appearance concerns. Parents rated older children and those on dialysis longer as functioning worse on multiple global and disease-specific (e.g., fatigue, relationship) domains. Parents also rated children as functioning increasingly worse in school over time. Further, patient ESRD history (acute onset vs. medically managed) impacted how parents viewed the burden of ESRD on their child over time.