Acceleration of comorbid illness in patients undergoing long-term maintenance hemodialysis may be manifested by clinical deterioration that is subtle and not immediately life-threatening. Nonetheless, it is emotionally debilitating for patients and families in addition to being medically and ethically challenging for treating nephrologists. A marked decline in clinical status warrants review of the balance of benefits to burdens dialysis is providing to a given patient and should trigger conversation about the option of withdrawal using an individualized patient-centered, rather than disease-oriented, approach. This paper presents a rationale for and an objective approach to initiating and managing dialysis withdrawal for patients who wish to withdraw because of unsatisfactory quality of life and those (many with significant cognitive impairment) for whom withdrawal is deemed appropriate because the burdens of continuing treatment substantially outweigh the benefits.