Remarkable advances in modern biology have enhanced our understanding of disease, permitting us to define-and potentially to treat-illness at the cellular and molecular level. The challenge we now face as physicians and physician-scientists is ensuring that these advances find expression in clinical practice. Thus far, the distance from the bench to the bedside has been surprisingly difficult to span, reflecting the need to develop broader, more integrative approaches to understanding how component molecules and physiologic systems function in the context of the whole person. Although there appears to be a consensus about the need to pursue such integrative, patient-oriented research, a mechanism for training future investigators in this discipline is less well established. In this essay, we present and develop the rationale for a set of underlying principles for patient-oriented research that can be used to guide appropriate training in this field. We also describe briefly a recently established prototype program-the Harvard initiative in Patient-Associated Science: Training, Education, Understanding, and Research (PASTEUR)-that we hope will help cultivate patient-oriented investigators and catalyze the evolution of patient-oriented research into a fully realized academic discipline.