Living donor kidney transplantation (LKD) has to be considered the best transplant choice for ESRD patients in terms of organ quality and survival. ABO incompatibility and positive cross-match frequently impede LKD. Recently, options based on stronger immunosuppression, apheresis techniques and Ig administration have been proposed to overcome the biological barriers. International guidelines on LKD advise paired exchange as the preferable transplant option to avoid the hazard of blood type or cross-match incompatibility. Since 1986 many paired exchange LKD programs have been started in the world including the USA, Japan, South Korea and, in Europe, the Netherlands, Switzerland, Romania, Germany and Italy. The first Italian paired exchange LKD was performed at the Pisa Transplant Center in November 2005 between three couples of spouses. One year later a National Program was established by the Italian National Transplant Center. The second experience in Italy was again in Pisa in December 2007 between two couples of spouses. International reports have shown that paired exchange LKD offers good clinical results comparable to direct LKD. In our experience paired exchange LKD is to be considered a quality choice for uremic patients, in that it allows them to obtain the benefit of an LKD that would otherwise not be practicable.