The gold standard to assess the compliance of hemodialysis (HD) patients has not been established. Compliance parameters should be easily measured and verified, reproducible, clearly interpretable, and accurate. They should have meaning for the patient, clear pathophysiological significance unrelated to other factors, and be related to important outcomes. There is poor correlation of subjective and objective measures and poor correlation of laboratory compliance measures. Different factors have been associated with differential compliance in different patient populations, depending on the measures assessed. Recently, behavioral measures of compliance with dialysis prescription, such as shortening or skipping HD treatments, have been developed. New data confirm that many compliance measures, including both laboratory and behavioral compliance indices, are associated with patient outcomes. It is the duty of the nephrologist and staff to make the importance of compliance understandable to patients. It is important for the health care team to understand patients' expectations and attitudes about their illness and their beliefs about the efficacy and importance of the treatment, as well as patients' demographic, medical, psychological, familial, and socioeconomic status, before realistically evaluating compliance. Such knowledge and approaches may be critical in achieving mutually agreed on compliance goals. We suggest that although assessment of indirect indices is useful, behavioral compliance measures that quantify shortening and skipping behaviors generally should be used in HD patients. Hopefully, analyses of results that control for multiple potentially confounding factors and effective interventions to improve compliance will be developed in the near future.