Careful evaluation of potential living kidney donors is crucial to assure the well being of the donors, especially because they do not gain any direct medical benefit from donation. This process also helps assess the quality and safety of the organs donated to the recipients. While all programs share these goals, donor selection criteria vary significantly among U.S. transplant centers. In part, this is due to the limited data that exists as to long-term outcomes among donors who are medically complex, or at higher risk for complications, such as those with hypertension, obesity, or lower kidney function. This article reviews available evidence regarding outcomes after living donation and current trends in U.S. practices, and seeks to provide practical guidance in evaluating high-risk potential living kidney donors.