Contrast agents were introduced early in the history of medical imaging. Iodine-based intravascular agents became the radiographic compounds of choice and refinements of their chemical structures led to the highly tolerated low-osmolarity agents in use today. Gadolinium became the most popular compound for MR imaging; however, recognition of nephrogenic systemic fibrosis and in vivo dechelation intensified research on their safety profile. Ultrasonography contrast media evolved from manual injections of air through agitated saline solutions to microbubbles with different gases. Research has concentrated on bubble stabilization and development of small but sufficiently echogenic particles.