The invention of dialysis has been a phenomenal advance in the treatment of kidney failure. The introduction of artificial kidneys in clinical care remains one of the most successful lifesaving interventions in modern medicine. Its glory, however, has been tempered by poor long-Term outcomes and a negative qualitative impact on the lives of patients who suffer from an extremely complex, burdensome, and restricted life on dialysis. There remains a huge gap in patient well-being and outcomes between artificial kidney treatments and kidney transplantation. The inadequacy of dialysis, at least in part, is due to the chronic accumulation of organic retention solutes of middle and large molecules in chronic kidney disease, which are poorly removed by current dialytic treatment modalities. Incremental benefits observed through alternative strategies such as high volume hemodiafiltration, high frequency, and expanded hemodialysis (HD) schedules have had limited success, due to a host of organizational, complex technology need and human factor barriers. Expanded HD (HDx) therapy offers a novel blood purification technology, with the use of high retention onset (HRO) membranes designed to achieve a superior spectrum of solute waste removal in uremia. Limited studies have demonstrated the potential benefit of HRO membranes in reducing cardiovascular risk, vascular calcification, and inflammation commonly associated with the "residual uremic syndrome" and patient symptom burden. Robust and efficient clinical trials are now required to establish the rationale and impact of HDx therapy in driving improvements in both physician-and patient-directed clinical goals and outcomes in dialysis.