Contrast Agents (CA) are among the most commonly prescribed drugs worldwide, and are used, with a variety of techniques, to increase and intensify the differences between body tissues and to help radiologist make diagnoses in a fast and precise way. In recent decades, advancements in research have resulted in significant improvements in their composition, and have made them safer and better-tolerated by patients; this notwithstanding, although the currently available CA are generally considered to be safe, their use is not completely without risk. The use of CA faces the radiologist with economic considerations, bioethical dilemmas, and possible profiles of professional responsibility. In fact, to achieve the best results in diagnostic imaging, radiologists have to focus on making an appropriate choice of CA, in consideration of efficacy, safety and appropriateness. Moreover, besides by cost/benefit models widely introduced in health management, radiologists are also influenced by their responsibility of appropriate use for the various diagnostic tests and, finally, the choice of best CA to utilise for each individual patient. Thus, the dilemma of choosing between the best and the most cost-effective tests and procedures is occurring more frequently every day. Different variables, such as the patient, examinations, and technology available, can affect the choice of CA in terms of obtaining the highest diagnostic quality, minimum impact on higher-risk patients, and optimisation of used volumes and injection flows.