Clinical epidemiology applies the concepts and techniques of epidemiology, statistics, and decision analysis to clinical problems. Clinical epidemiology emphasizes the study of patients, physicians, and systems of health care. The focus is on diagnosis, prognosis, and treatment of disease but it also studies the etiology of disease. Exposures and outcomes are informed by clinical and biologic knowledge as well as broader environmental and societal determinants. Distinctive areas of clinical epidemiology are the development of diagnostic and prognostic models. The gold standard for the study of medical treatments is the randomized clinical trial. Observational analyses of treatments are necessary to gain estimates of their impact in real world clinical practice and to screen for rare effects. These observational analyses of medical interventions face the distinctive hurdle of confounding by indication and/or contraindication.