Medical education is at a crossroads. Although unique features exist at the undergraduate, graduate, and continuing education levels, shared aspects of all three levels are especially revealing, and form the basis for informed decision-making about the future of medical education.This paper describes some of the internal and external challenges confronting undergraduate medical education. Key internal challenges include the focus on disease to the relative exclusion of behavior, inpatient versus outpatient education, and implications of a faculty whose research is highly focused at the molecular or submolecular level. External factors include the exponential growth in knowledge, associated technologic ("disruptive") innovations, and societal changes. Addressing these challenges requires decisive institutional leadership with an eye to 2020 and beyond--the period in which current matriculants will begin their careers. This paper presents a spiral-model format for a curriculum of medical education, based on disease mechanisms, that addresses many of these challenges and incorporates sound educational principles.