CT scans use iodinated contrast media (ICM) to increase enhancement of soft-tissue structures. Some techniques, such as CT angiography, accentuate specific anatomy. The chemical structure of ICM is rich in iodine. Because of iodine's high atomic number, use of ICM causes an increase in CT number and image contrast. Improper contrast enhancement is a leading motivator for both repeated CT examinations and those with limited or suboptimal diagnostic utility. Optimization of contrast agent administration is essential to avoid poor enhancement. Many interacting factors affect contrast enhancement and can be divided into three main categories: physics-based, patient-related, and contrast protocol-based factors. Physics-based factors include tube potential, beam hardening, and scan duration. Patient-related factors include blood volume and cardiac output. Contrast protocol-based factors include contrast agent volume, injection rate, iodine concentration, scan delay, and saline flush. These factors can be further stratified into scalar, temporal, and sampling factors. Scalar factors change the magnitude of enhancement by a fixed percentage independent of time (eg, changing tube potential or iodine concentration). Temporal factors modify the temporal dynamics of contrast enhancement (eg, changes in cardiac output or injection rate). Sampling factors affect how an ICM enhancement curve is sampled (eg, scan duration, scan delay). Understanding the available parameters and their impact on ICM enhancement equips the reader with tools to optimize contrast agent delivery and scanning protocols in CT.