Adenovirus (Ad)-based vectors are considered a promising tool for effective gene transfer in a number of renal disease-specific applications. This opinion is based upon their natural ability to infect a broad array of both dividing and terminally differentiated, nondividing cell types, their capacity to deliver (transduce) large amounts of DNA, and the ease at which this vector platform can be mass produced. Furthermore, Ads remain the gene transfer vector of choice for numerous human clinical trials, as more clinical trials utilize Ad-based vectors than any other vector currently available. However, as with all types of gene transfer vectors, several limitations to the use of Ads have been delineated. The construction of advanced-generation Ad vectors with unique modifications of the viral genome has addressed many of these issues, although continued research will no doubt provide safer alternatives to the presently used viral vectors. In this chapter, we review the current state of Ad-based gene transfer, brief updates on advanced-generation Ad-based vectors, and provide a discussion of how these vectors infect various tissues. We then specifically focus on the kidney and discuss a multitude of techniques previously employed to deliver Ad-based vectors to various regions of the kidney and in the process, reveal many associated complexities. Furthermore, exciting new studies that use Ads to express immunosuppressive gene products have shown great promise in the area of transplantation and allograft survival. Based upon this summary, we confirm that Ad-based vectors currently offer multiple advantages for the study and potential treatment of a great variety of renal and urological diseases. Utilization of advanced-generation Ad vectors combined with novel insights into the complexities of Ad-based gene transfer in general, should allow numerous inroads to be made in the near term, relative to the use of Ad-based gene transfer to treat a variety of renal diseases.