Once a research question or hypothesis has been derived, the investigatormust determine which research methodology can best answer his or her question. Prospective, randomized, controlled trials are often considered the sine qua non of research design. However, this study design is not always feasible, and often an alternate design will adequately answer the question at significantly less cost. All research designs have potential advantages and limitations. The decision of which study design to use is often a compromise between science and resources. This article was prepared by members of the SAEM Research Committee to describe the fundamental research concepts of research design. This paper defines different research methodologies and discusses their different uses, strengths, and weaknesses. It also describes the process of randomization and blinding. Finally, the concept of bias and its remedies is delineated.