Human subject studies or clinical trials of a medical device are often required before a new device can be sold in the marketplace. The goal of a human subject study is to show safety and efficacy of a new device. However, the history of using human subjects in experiments has had a checkered past, resulting in a mass of governmental regulation aimed at ensuring reasonable subject safety while enforcing reliable scientific method. This article offers a brief overview of the structure, relevant regulations, and major steps that make up a clinical trial. It defines the roles of the various participants and emphasizes the responsibilities required of the sponsor and the clinical investigator. A brief overview of relevant regulations, standards, and guidance documents is given, with specific links to useful websites. In addition, the different regulatory requirements of significant versus nonsignificant risk devices are discussed. Finally, a synopsis of the preparation, execution, and analysis and reporting of clinical studies is given. Human clinical trials are complex, but when methodical efforts are made to follow and comply with regulatory and scientific requirements, reliable data can be generated while treating human subjects in an ethical and safety-conscious manner.