Understanding the strengths and weaknesses of the control group used in a randomized clinical trial is essential because comparisons of outcomes between the investigational and control groups form the basis of inferences regarding the safety and efficacy of the investigational treatment. For its 2007 International Conference, the American Thoracic Society (ATS) sponsored a scientific symposium in which the strengths and limitations of different types of control groups in clinical trials of pharmacotherapy, procedures, devices, and behavioral interventions were discussed. In this section, the co-chairs of this ATS symposium provide an overview of the presentations, including a brief historical perspective on the use of control groups in clinical trials.