Historically, QT prolongation, occurring with or without drug therapy, has been considered primarily as a clinical marker for risk of arrhythmia. However, as understanding of cardiac repolarization improves and ability to measure accurately small changes in QT interval increases, the QT interval will be used as a marker for drug action as well. In addition, QT prolongation may prove to be a valuable tool for detecting and quantifying risk of arrhythmia due to drugs. This has been emphasized recently by the experience with terfenadine. Use of the QT interval as a marker for toxicity and efficacy will require sensitive and specific methods that are currently being developed and validated. The current methodologies for detecting small changes in the QT interval and the significance of those changes are discussed.