Clinical reasoning is a crucial determinant of physicians’ performance. It is key to arrive at a correct diagnosis, which substantially increases the chance of appropriate therapeutic decisions. Clinical teachers face the daily challenge of helping their students to develop clinical reasoning. To select appropriate teaching strategies, it may be useful to become acquainted with the results of the research on clinical reasoning that has been conducted over the last decades. This article synthesizes the findings of this research that help in particular to understand the cognitive processes involved in clinical reasoning, the trajectory that leads the student from novice to expert, and instructional approaches that have been shown to be useful to facilitating this trajectory. The focus of the article is the diagnostic process, because it is about it that most research has been conducted. This research indicates that there is not a particular reasoning strategy that is specific to expert physicians and could be taught to students. It is the availability of a large knowledge base organized in memory in illness scripts of different formats that explains the expert’s better performance. The more, the richer, and the more well-structured are the illness scripts a physician has stored in memory, the more he/she would be able to make accurate diagnoses. These scripts are formed gradually over the years of education. To help develop them, students should be exposed to a wide variety of clinical problems, with which they must interact actively. Instructional approaches that require students to systematically reflect on problems, analyzing differences and similarities between them, explaining underlying mechanisms, comparing and contrasting alternative diagnoses, have proved useful to help refine disease scripts. These approaches are valuable tools for teachers concerned with the development of their students clinical reasoning.