The search for better radiopaque iodinated contrast material for intravascular use is continuing, but the recent development of new lower osmolality contrast media (LOCM), both ionic and nonionic, has dramatically affected the practice of radiology. The major issue retarding the introduction of LOCM into clinical practice in this country has been the increased cost of the media. Numerous preliminary assumptions and probabilities about the tolerance, efficacy, and overall safety of LOCM have been documented in scientific studies. The lower osmolality, reduced chemotoxicity, and high hydrophilicity of new compounds, particularly the nonionic variety compared with conventional high osmolality ionic agents (HOCM), offer a significant margin of safety to patients with known risk factors. Mounting data suggest that low or no risk patients are benefited as well, perhaps to an even greater degree. Costly trade-offs to the universal use of LOCM exist, therefore careful consideration of the advantages and disadvantages of LOCM for intravascular administration is required. This article, presented as the Preston M. Hickey Memorial Lecture to the Michigan Radiological Society in March of 1990, explores the historical development of iodinated intravascular contrast media, especially LOCM, and cites existing data that form the basis for various strategies for their use, that is, selective, universal, or nonvascular use. Better, safer, and less expensive contrast media are a realistic expectation in this new decade of technological promise. Reducing adverse side effects from the use of any new drug or technology must be our continued, collective goal.