Academic medical centers (AMCs) face challenges to the achievement of their potential in clinical research. These challenges include reduced support of research from clinical revenue, cultural impediments to clinical research within the traditional value system of research-intensive AMCs, and potential problems of patient access to clinical research in intensive managed care environments. This article considers options to strengthen clinical research that have been developed at some medical centers. While much attention is being directed to the expansion of clinical trials in many AMCs, this effort needs to be linked to a cohesive strategy for clinical research being conducted in an academic environment. The article also addresses the subject of training and career development. It concludes with the opinion that the "crisis" in clinical research in academic medical centers provides the opportunity to define, more explicitly, the nature and scope of the investment in clinical research, and to define strategies that will bring added value to knowledge generated from basic research and to the teaching and patient care missions of these centers.