There is overwhelming evidence that individuals with Major Depressive Disorder (MDD) are being seriously under diagnosed and under treated. The Self-Reporting Questionnaire (SRQ) is a good screening instrument for the detection of psychiatric disorders. However, the clinical significance of SRQ as a screening test for MDD in patients on hemodialysis (HD) has yet to be elucidated. The purpose of this study was to evaluate the diagnostic utility of the SRQ in detecting MDD in a cohort of patients with end-stage renal disease (ESRD) on maintenance HD. Twenty-six patients on maintenance HD were randomly recruited and were asked to complete the SRQ. The participants were, in addition, interviewed by a psychiatrist, who had been blinded to the SRQ score. We examined the ability of SRQ to detect patients who were diagnosed to have MDD based on psychiatric assessment. Among the 26 patients assessed, four patients were diagnosed to have MDD based on current diagnostic criteria. Logistic regression analysis showed that SRQ could predict patients with MDD with adjusted odds ratio of 1.9 (CI, 1.06- 3.42). Being a female was the most important variable for having a high SRQ (F=16.9, P=0.0004). The limitations of this study include a relatively small sample size and a high rate of somatic symptoms reported in the non-depressed population that limited the positive predictive value of the SRQ. Thus, although the SRQ has a high sensitivity, the positive predictive value of the SRQ is poor at low cut offs. In conclusion, our study suggests that an ideal screening tool in patients on HD should have minimal emphasis on the somatic symptoms of MDD. Until such a tool is available, clinical assessment remains the best screening tool for MDD.