End-stage renal disease (ESRD) remains a risk factor for increased morbidity and mortality. Dialysis counteracts its immediate life-threatening complications, but does not provide for a comparable homeostasis to that of a normal kidney, accelerates atherosclerosis, and induces inflammatory changes that also predispose patients to cardiovascular death. Kidney transplantation (KT) results a cost-effective alternative to dialysis for the management of ESRD, providing for improved survival and quality of life. A large proportion of patients with ESRD suitable for a KT are relatively young. Therefore, kidney transplantation is also one of the most satisfying areas of medical practice today. However, KT goes further just the technical operative aspects. Therefore, every physician involved in KT should have a deep knowledge on these aspects too. This chapter reviews the different medical aspects of both the donated kidney allograft and potential recipient of a KT, including an updated discussion on kidney allograft preservation and pre-transplantation diagnosis, different aspects regarding immunossupression and its consequences, and all the issues regarding how to perform an adequate follow-up after the procedure.