Iodinated contrast is a mainstay for diagnostic and interventional procedures performed by cardiologists, radiologists and other specialists. With the emergence of computed tomographic techniques for the evaluation of cardiac disease, malignancies, trauma and a variety of other internal disorders, the use of iodinated contrast is expected to increase dramatically over the next few years. There has been considerable refinement over the past decades from ionic high-osmolar, to nonionic low-osmolar and finally to nonionic iso-osmolar contrast. Iodixanol is the only nonionic iso-osmolar contrast approved for intravascular use. This contrast agent has the lowest rates of systemic and renal adverse events. Clinical trials have demonstrated the lowest rates of contrast-induced nephropathy among all currently available forms of iodinated contrast. Specifically, iodixanol has been associated with a 71% relative risk reduction for contrast-induced nephropathy compared with low-osmolar agents in head-to-head randomized trials. This article reviews the structure, pharmacology and outcomes associated with iodixanol.