There are valid scientific and ethical considerations for using a control group in a clinical trial. Placebo-controlled trials are justifiable when they are supported by sound methodologic consideration and when their use does not expose research participants to excessive risk of harm. Consideration should be given to "best available therapy" control groups in the evaluation of a new therapy or intervention over an existing therapy. Investigators should keep in mind that one should not sacrifice the scientific merit of a trial to include a best-available-therapy control group as long as the placebo control group poses little harm to participants and, importantly, the trial offers potential benefit to the subject. The pros and cons of using placebo versus best-available-therapy control groups are discussed.