The ability to take a comprehensive and accurate clinical history, perform a thorough and nuanced physical examination, engage in sequential clinical reasoning using all relevant clinical and laboratory data, and communicate clearly and compassionately with patients and other providers—the skills of the clinical transaction—are critical to a successful therapeutic outcome. Yet few medical schools’ curricula include an explicit focus on developing these skills beyond the introductory level. Vanderbilt Medical School has developed a structured curriculum, integrated into the traditional clerkships of the third and fourth years, that ensures that each student receives specific instruction in clinical transaction skills. The clinical transaction curriculum is based on a set of 25 presenting problems, with learning objectives identified for each problem. Primary responsibility for instruction relating to each presenting problem is assigned to specific core clerkships, with the major portion of teaching provided by a nucleus of specially selected and compensated master clinical teachers. The Clinical Transaction Project at Vanderbilt was begun in 2004. Future development will focus on enhancing approaches to student assessment.