Each episode tells the stories of two patients who experienced difficult to diagnose medical conditions. Each segment generally begins with a short description of the patient's life before they fell ill (or in the case of a young child, the parents' life before the child was born). The symptoms that the person experienced are described from their onset, usually becoming progressively worse; the progression is often re-enacted by actors while the original patient narrates. The show chronicles the patient's visits from doctor to doctor, where they may receive misdiagnoses or be told that the doctors have found nothing wrong. After continuing to experience symptoms for an extended period of time, the person discovers a doctor who is able to solve their case. The doctor reviews the patient's medical records, notices a symptom that his or her colleagues overlooked, performing tests, and finally reaching the correct diagnosis and giving the proper treatment. This is followed by a brief explanation of why the disorder was so difficult to diagnose, and a description of what the person's life is like today. Usually, the patient is still alive. Some have died after the episode was taped or aired, and only one has died before the diagnosis (though his afflicted brother survived).