Recent approaches to reducing radiation exposure during CT examinations typically utilize automated dose modulation strategies on the basis of lower tube voltage combined with iterative reconstruction and other dose-saving techniques. Less clearly appreciated is the potentially substantial role that iodinated contrast media (CM) can play in low-radiation-dose CT examinations. Herein we discuss the role of iodinated CM in low-radiation-dose examinations and describe approaches for the optimization of CM administration protocols to further reduce radiation dose and/or CM dose while maintaining image quality for accurate diagnosis. Similar to the higher iodine attenuation obtained at low-tube-voltage settings, high-iodine-signal protocols may permit radiation dose reduction by permitting a lowering of mAs while maintaining the signal-to-noise ratio. This is particularly feasible in first pass examinations where high iodine signal can be achieved by injecting iodine more rapidly. The combination of low kV and IR can also be used to reduce the iodine dose. Here, in optimum contrast injection protocols, the volume of CM administered rather than the iodine concentration should be reduced, since with high-iodine-concentration CM further reductions of iodine dose are achievable for modern first pass examinations. Moreover, higher concentrations of CM more readily allow reductions of both flow rate and volume, thereby improving the tolerability of contrast administration.