Characterization of renal transplant recipients as "high-risk" originated in the 1970's, although attributes that defined this category, such as diabetes mellitus, are no longer applicable. The changing paradigm of risk after renal transplantation reflects the impact of nonspecific advances in clinical care, specific interventions that address previously defined problems, changing demographics, and new issues that have arisen as a consequence of changes in clinical practice. In the current era, diabetes, retransplantation, and presensitization are no longer considered risk factors for poor outcomes after kidney transplantation. Significant risk factors influencing intermediate-term graft survival now include donor and recipient age over 60 years, DR mismatching (only in kidneys from deceased donors), time awaiting transplantation, and African-American race. Current clinical approaches to care of the renal transplant candidate/recipient focus on minimizing the impact of identified risk factors rather than avoiding transplantation altogether. For most ESRD patients, the greatest risk lies in not receiving a transplant.