Defining rational follow-up guidelines in patients treated for cancer is important, from both a medical and an economical perspective. Renal-cell carcinoma is reputed to be unpredictable in its course and only a few, and often contradictory, follow-up guidelines exist for patients treated for nonmetastatic renal-cell carcinoma. Recent advances in tumor biology have contributed to a better understanding of this cancer and have indicated that personalized follow-up regimens, based on tumor and host molecular characteristics, might be possible in the near future.