The importance of clinical research for the practice of clinical medicine is immense and undeniable. Yet the type of knowledge gained from clinical research, referred to here as "empirical evidence," is itself insufficient to provide for optimal clinical care. A gap exists between empirical evidence and clinical practice. Proponents of evidence-based medicine have clearly acknowledged one aspect of this gap: the part that requires the consideration of values, both patient and professional, prior to arriving at medical decisions. Not as clearly recognized, however, is the gap that exists due to the fact that empirical evidence is not directly applicable to individual patients, as the knowledge gained from clinical research does not directly answer the primary clinical question of what is best for the patient at hand. Proponents of evidence-based medicine have made a conceptual error by grouping knowledge derived from clinical experience and physiologic rationale under the heading of "evidence" and then have compounded the error by developing hierarchies of "evidence" that relegate these forms of medical knowledge to the lowest rungs. Empirical evidence, when it exists, is viewed as the "best" evidence on which to make a clinical decision, superseding clinical experience and physiologic rationale. But these latter forms of medical knowledge differ in kind, not degree, from empirical evidence and do not belong on a graded hierarchy. As they differ in kind, these other forms of medical knowledge can be viewed as complementary to empirical evidence and their incorporation necessary to overcome the intrinsic gap noted above. Clinicians, then, need to incorporate knowledge from 5 distinct areas into each medical decision: (1) empirical evidence, (2) experiential evidence, (3) physiologic principles, (4) patient and professional values, and (5) system features. The relative weight given to each of these areas is not predetermined, but varies from case to case.