You are a primary care physician seeing a 53 year old man who was examined 2 days ago in an emergency department for an episode of syncope. He had been waiting in a long queue when he felt lightheaded and nauseated; then he lost consciousness, with no witnessed seizure activity. He has been healthy, with no known cardiac or neurological disease. In the emergency department, his vital signs and findings on cardiac and neurological examinations had been normal, as were his blood count, blood glucose concentration, and 12 lead electrocardiogram. He was given no diagnosis, and he is now worried about what caused this episode and whether it will recur. Of the many causes of syncope, you wonder which should be sought in this patient.

“Differential diagnosis” refers to the methods by which we consider the possible causes of patients' clinical findings before making final diagnoses.^{1, 2} At its heart, differential diagnosis involves acts of selection: we consider a patient's illness and choose which disorders to pursue further. Is there high quality research that could guide our selections, such as evidence about the frequency of disorders that can cause clinical problems like syncope? If so, wouldn't it be grand if someone would find it, summarise it, and tell us about it?

Beginning with this issue, Evidence-Based Medicine will do just that—search for the best new evidence about differential …