An active control is an intervention, such as a drug, a therapy, or a medical device, whose effectiveness has previously been established. Active controls have been used in trials with or without a placebo. For clinical drug trials with a placebo, active controls usually play a secondary role with respect to demonstrating the effect of a new treatment. In placebo control trials involving psychotropic agents (Leber1&21, 2), active controls are intended for the purpose of verifying the assay sensitivity of the trial, i.e., the ability of the trial to demonstrate an effective drug to be effective (ICH-E103). In this article, an active control trial refers specifically to a trial with an effective intervention or treatment as the control, without the presence of a placebo. Active control trials often arise when the objective of a trial is to investigate the effect of the new treatment on mortality or serious morbidity outcome for patients with certain serious diseases. For obvious ethical reason, when there are available known effective treatments for the disease, one should use one of these active treatments instead of a placebo as the control (Declaration of Helsinki4). In the interest of clarity and without much loss in generality, the concepts and issues will be discussed here within the framework of a blinded, parallel, randomized trial comparing the survival experience of a new treatment, T, to a single active control, C, in treating patients with certain serious diseases.