Under the auspices of the United Network for Organ Sharing, the American Society of Transplant Surgeons and the American Society of Transplantation, a meeting was convened on May 25, 2006, in Washington, DC, to develop guidelines for the psychosocial evaluation of prospective living kidney donors who have neither a biologic nor longstanding emotional relationship with the transplant candidate. These ‘unrelated’ donors are increasingly often identified by transplant candidates via the Internet, print media and other public appeals. The expansion of living donor kidney transplantation to include significant numbers of donors with little to no preexisting relationship to the candidate has caused concern in the medical community regarding such psychosocial factors as donor psychological status, motivation, knowledge about donation and the potential for undue pressure to donate under some circumstances. Therefore, experts in mental health; psychosocial, behavioral and transplant medicine; and medical ethics met to specify (a) characteristics of unrelated donors that increase their risk for, or serve as protective factors against, poor donor psychosocial outcomes, (b) basic principles underlying informed consent and evaluation processes pertinent to these donors and (c) the process and content of the donor psychosocial evaluation. The meeting deliberations resulted in the recommendations made in this report.