A review is given of the development of the water-soluble contrast media (CM) with particular attention to the frquency of neurological complications. A remarkable improvement was achieved following the introduction of the nonionic agent metrizamide in 1974, and a further decrease in neurotoxicity was obtained with the newer nonionic monomers, which have multlple hydroxyl groups included at different sites of the molecule. Theoretical considerations and experimental studies suggest that the neurotoxicity of the new nonionic dimeric agents shuold be at least within the low range seen with the monomeric ones, but further experience is needed before definite conclusions can be drawn in this respect. The mechanisms responsible for the neurological complications seen with CM are unknown but certain critical groups on the CM molecules are known. Several animal models have been developd, which may help predict the degree of neurotoxicity.