The confluence of an increasing prevalence of end-stage renal disease (ESRD), clinical trial data suggestive of benefit from quotidian dialysis, and ongoing cost/benefit reanalysis of healthcare spending have stimulated interest in technological improvements in provision of ESRD care. For the last decade, our group has focused on enabling technologies that would permit a paradigm shift in dialysis care similar to that brought by implantable defibrillators to arrhythmia management. Two significant barriers to wearable or implantable dialysis persist: package size of the dialyzer and water requirements for preparation of dialysate. Decades of independent research into highly efficient membranes and cell-based bioreactors culminated in a team effort to develop an implantable version of the University of Michigan Renal Assist Device. In this review, the rationale for the design of the implantable artificial kidney is described.