Successful renal transplantation is a highly effective endeavor that improves and prolongs the lives of patients with chronic kidney disease. Transplant surgery and immunosuppression carries risk and the demand for donor kidneys outstrips supply by far. These realities mandate thoughtful allocation and utilization of this limited resource to select candidates. As the criteria for candidates and donor grafts continue to expand, the field must adapt and seek new approaches. The complex process—from evaluation of candidates, transplant surgery, immunosuppression, and follow-up care after transplantation—is, of necessity, tightly structured and regulated. However, each patient has distinctive characteristics that must be taken into account to optimize individual outcomes. The personalized approach to renal transplantation, which uses precision medicine concepts, identifies unique aspects of candidates/recipients that require consideration using a combination of time-honored guidelines, emerging concepts, new medications, and refinements of care.