The patterns of patient referrals, the guidelines for diagnostic procedures and treatment, and the academic leadership have continued to change in the last two decades. The revolution brought about by molecular biology has dramatically changed the pace and direction of medical research during this period. In addition, the introduction of managed care competition in the past decade has dramatically challenged the practice of medicine. The effects of all these changes on nephrology and some lessons learned from developing and leading a regional pediatric nephrology program will be discussed. The role of the National Institutes of Health in changing research focus will be examined. These observations may be useful to those preparing to meet the challenges of clinical care and research in this competitive era.