The continuing advances in computed tomographic (CT) technology in the past decades have provided ongoing opportunities to improve CT image quality and clinical practice and discover new clinical CT imaging applications. New CT technology, however, has introduced new challenges in clinical radiology practice. One of the challenges is with intravenous contrast medium administration and scan timing. In this article, contrast medium pharmacokinetics and patient, contrast medium, and CT scanning factors associated with contrast enhancement and scan timing are presented and discussed. Published data from clinical studies of contrast medium and physiology are reviewed and interpreted. Computer simulation data are analyzed to provide an in-depth analysis of various factors associated with contrast enhancement and scan timing. On the basis of basic principles and analysis of the factors, clinical considerations and modifications to protocol design that are necessary to optimize contrast enhancement for common clinical CT applications are proposed.