Each day, we generate hypotheses about our environment—our perceptions of people, our expectations of events, and our interpretation of images. These hypotheses provide a framework by which we interpret our experiences. The same is true for differential diagnosis by which health care practitioners develop hypotheses or diagnoses from a set of cues provided during an encounter with a patient. For clinicians to be successful at differential diagnosis, they must use a multidimensional and complex process involving nonanalytic and analytic cognitive processes and metacognition—thinking about thinking. Our conclusions, however, can lead to errors in diagnosis. Many of these errors are due to errors in cognition. The purpose of this article is to discuss this complex process, identify common errors in cognition, and offer strategies to prevent these common errors in differential diagnosis.