Hemodialysis patients use a variety of oral medications on a daily basis to control their kidney disease and comorbid illnesses. Under the new paradigm of kidney disease care for dialysis units outlined in the 2008 US Centers for Medicare & Medicaid Services Conditions for Coverage, there has been a formal shift in the role of the hemodialysis patient from a passive participant in care planning to a fully collaborative member of the interdisciplinary team. In the chronic disease care field, the focus from patient compliance or patient adherence to patient self-management complements this paradigm shift in dialysis care. In this narrative review, we discuss key barriers to adult hemodialysis patient self-management of oral medications that include pill burden, demographic and socioeconomic variables, psychosocial factors, health literacy, patient satisfaction, and health beliefs. We further examine these barriers in the context of the 2008 Medicare Conditions for Coverage. To promote hemodialysis patients' self-management of oral medication regimens, additional research and behavioral interventions are needed to help hemodialysis patients overcome obstacles that impede their ability to effectively manage chronic illness and improve health outcomes.