Clinical research in neurology may be based on observation or intervention. Basic science and observational clinical studies often address questions of cause and pathogenesis, whereas interventional clinical experiments normally are required to establish the safety, tolerability, and efficacy of therapies. This article outlines various study paradigms and discusses the concepts of intervention, randomization, blinding, and control in the context of clinical trial design. Accurate interpretation of trial results is predicated on the care with which experimental therapeutic studies are designed and conducted.