The USMLE assesses a physician's ability to apply knowledge, concepts, and principles, and to determine fundamental patient-centered skills that are important in health and disease and that constitute the basis of safe and effective patient care. Examination committees composed of medical educators and clinicians from across the United States and its territories create the examination materials each year. At least two committees critically appraise each test item or case, revising or discarding any materials that are in doubt.

USMLE exam consists of a series of patient encounters in which the examinee must see standardized patients (SPs), take a history, do a physical examination, determine differential diagnoses, and then write a patient note based on their determinations. The topics covered are common outpatient or Emergency Room visits which are encountered in the fields of internal medicine, surgery, psychiatry, pediatrics, and obstetrics and gynecology. Examinees are expected to investigate the simulated patient's chief complaint, as well as obtain a thorough assessment of their past medical history, medications, allergies, social history (including alcohol, tobacco, drug use, sexual practices, etc.), and family history. Usually, examinees have one telephone encounter, speaking to an SP through a microphone during which there is no physical exam component.
Examinees are allowed 15 minutes to complete each encounter and 10 minutes for the patient note for a single patient encounter. The patient note is slightly different from a standard SOAP note. For the exam note, the examinees will document the pertinent facts relating to the history of present illness as well as elements of the past medical history, medication history, allergies, social history, family history, and physical exam. The examinees will then state up to 3 differential diagnoses relating to the simulated patient's symptoms, and tests or procedures to investigate the simulated patient's complaints. The examinees should also list pertinent positive and negative findings to support each potential diagnosis. The examinees will not recommend any specific treatments in the note in contrast to a true clinic SOAP note (i.e., IV fluids, antibiotics, or other medications). Over the course of an 8-hour exam day, the examinees complete 12 such encounters. Examinees are required to type patient notes on a computer.