Background: Chronic kidney disease (CKD) is a global public health issue with an estimated prevalence of 8-16% worldwide. End-stage renal disease eventually develops every year in 0.15-0.2% of patients with overt CKD, and renal replacement therapy (RRT) with dialysis or transplantation is required. Although approximately 2 million people worldwide are currently on RRT to sustain life, this likely represents less than 10% of those who need it. The kidney transplant approach is also seriously impaired by limited graft survival and by the scarce availability of donors. Innovative tissue-engineering strategies have been recently proposed to overcome these challenges. It is anticipated that these novel approaches will also be cost-effective in the long term. Although the initial setup of these innovative technologies could be quite expensive, there would be a single application for each patient, with no additional costs thereafter, compared to the lifelong costs of dialysis or immunosuppressive medications required for transplantation. One of the most innovative tools currently being investigated in experimental models is based on the idea of using decellularized kidneys to engineer a new functional organ as a potential future treatment option for end-stage renal disease. Summary: In the last 5 years, several interesting observations have been reported regarding the possibility of using an acellular matrix from the whole kidney and the attempt to recellularize this scaffold using stem or differentiated cells. This review provides an overview of the decellularization methods tested so far and their effects on the resulting extracellular matrix structure and composition. In addition, we also discuss methods recently described by us and others for the perfusion of kidney scaffolds for recellularization. Key Messages: Despite difficulties in achieving the import goal of kidney engineering in the laboratory, we discuss the problems with and limits of the experimental results obtained so far and point out the strategies that need to be adopted in order for this line of research to advance.