Adult-to-adult living donor liver transplantation (LDLT) is in a state of flux. Technical innovations and demand have outpaced internal and external regulatory efforts. This has led to a wide array of centers performing LDLT for a variety of indications without clear evidence on the risks to the donor or recipient or the system as a whole. The birth from necessity of LDLT in Asia has led to the extrapolation of the technique in America and Europe that has not been sufficiently studied in the appropriate populations. While there is a clear benefit in some patients, the appropriate donors and recipients have not been defined. Regulatory and ethical consideration should be focused on minimizing acceptable risk in donors and recipients and expanding the investigation into the costs and outcomes of this challenging procedure. The recently funded adult-to-adult living donor liver transplantation cohort sponsored by the National Institutes of Health aims to answer some of these questions over the next five years.