The four gadolinium chelates currently in clinical use as magnetic resonance imaging (MRI) contrast agents differ in two structural features: linear vs. macrocyclic cores, and ionic vs. nonionic charge types. While all are equivalent in relaxation effectiveness, the nonionic molecules have lower osmolality and viscosity and may be formulated safely at greater concentrations, and delivered confidently at greater doses and as a faster bolus. The macrocyclic molecules are more stable and show less tendency to dissociate free Gd. ProHance was conceived well over a decade ago, based upon a unique structure. It was first marketed in the USA in 1992, and was the first nonionic agent. It remains today still the only commercial MRI agent that is both macrocyclic and nonionic. To date it has been used safely in over a million patients.