Important advances in immunosuppressive therapy and refinement in surgical techniques have allowed renal transplantation to become the treatment of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life and, over time, can reduce the total cost of medical care. It must be noted, however, that although the risk of death in the first year after transplantation is <5%, not all patients qualify for the surgery because of their unacceptable risks for complications. The transplant evaluation process requires a comprehensive assessment of each patient’s medical, surgical, and psychosocial histories. Selection of the suitable transplant candidate remains a challenge for transplant physicians owing, predominantly, to the presence of complex medical issues in the potential candidates and nonstandardized criteria for acceptance or rejection among transplant centers. Furthermore, with the ever-increasing disparity between donor organ supply and demand and resultant increased wait-list times, the transplant physicians must further consider the optimal management and re-evaluation of wait-list patients during the waiting period. This article describes a systematic approach for the evaluation of a potential renal transplant candidate. Various medical issues that arise during the evaluation process are discussed.