Hemodialysis is the most common treatment for patients with end-stage renal disease (ESRD), and is required in many of these medically complex patients as a life sustaining option. Historically referred to as “renal replacement therapy”, the technique of hemodialysis has been continually refined overtime to provide better outcomes for patients. However, the rising prevalence of patients with ESRD and the limitations of current methods mandate further refinements in terms of both the device and the procedure. For instance, the limitations of currently available hemodialysis membranes include the tendency to occlude over time because of protein deposition and thrombus formation and the lack of portability. At present, the main functions of dialysis are to remove uremic toxins, maintain electrolyte balance, and restore fluid balance without addressing its other vital metabolic, endocrine, and immune functions. Therefore, it is crucial to have newer therapies that aim for complete replacement, not just clearance, and that focus not only on improved survival but also on patient-centric needs such as such as enhanced portability, the flexibility of therapy, reduced interventions, improved quality of life.