Health-related quality of life (HRQOL) is a valid marker of outcome for chronic dialysis therapy. A wide range of questionnaires are now available which assess different aspects of an individual's health. Appreciation of those factors that contribute to explaining HRQOL items remains poorly defined. The development of disease-specific questionnaires such as KDQOL-SF, should allow for such questions to be better answered. A cross-sectional analysis of our chronic dialysis population was made using the KDQOL-SF questionnaire. By multiple linear regression analysis demographic, clinical and dialysis-related factors were assessed for their contribution to the HRQOL in this population. The HRQOL of these patients was also compared against a general population sample. From a total of 190 chronic dialysis patients, 146 completed the KDQOL-SF questionnaire. The haemodialysis (HD) and peritoneal dialysis (PD) patients were similar with respect to most demographic, clinical and dialysis variables except for haemoglobin and albumin which were significantly (p < 0.05) greater in the peritoneal and haemodialysis populations respectively. Compared to the general population, the HRQOL of dialysis patients was impaired for all SF-36 subscales. Use of the disease-specific components of KDQOL-SF discriminated between dialysis modality for our dialysis population. Multiple linear regression analysis demonstrated that 27.5 to 42.7% of the variance in the SF-36 subscales could be explained. Satisfactory sleep, dialysis related symptoms, effect of kidney disease on lifestyle and burden of kidney disease were found to be the most important determinants of HRQOL for this population.