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Living kidney donation represents the best treatment for end stage renal disease patients, with the potentiality to pre-emptively address kidney failure and significantly expand the organ pool. Unfortunately, there is still limited knowledge about this underutilized resource. The present review aims to describe the general principles for the establishment, organization, and oversight of a successful living kidney transplantation program, highlighting recommendation for good practice and the work up of donor selection, in view of potential short- and long-terms risks, as well as the additional value of kidney paired exchange programs. The need for donor registries is also discussed, as well as the importance of lifelong follow up.