The first successful living-donor kidney transplant was performed 50 yr ago. Since then, in a relatively brief period of medical history, living kidney transplantation has become the preferred treatment for those with ESRD. Organ replacement from either a live or a deceased donor is preferable to dialysis therapy because transplantation provides a better quality of life and improved survival. The advantages of live versus deceased donor transplantation now are readily apparent as it affords earlier transplantation and the best long-term survival. Live kidney donation has also been fostered by the technical advance of laparoscopic nephrectomy and immunologic maneuvers that can overcome biologic obstacles such as HLA disparity and ABO or cross-match incompatibility. Congressional legislation has provided an important model to remove financial disincentives to being a live donor. Federal employees now are afforded paid leave and coverage for travel expenses. Candidates for renal transplantation are aware of these developments, and they have become less hesitant to ask family members, spouses, or friends to become live kidney donors. Living donation as practiced for the past 50 yr has been safe with minimal immediate and long-term risk for the donor. However, the future experience may not be the same as our society is becoming increasingly obese and developing associated health problems. In this environment, predicting medical futures is less precise than in the past. Even so, isolated abnormalities such as obesity and in some instances hypertension are no longer considered absolute contraindications to donation. These and other medical risks bring additional responsibility in such circumstances to track the unknown consequences of a live-donor nephrectomy.