Contrast agents are used as diagnostic molecules for the visualization of the vascular system. Despite their rapid pharmacokinetic distribution, and their excretion within a few minutes, their injection is associated with clinical symptoms of relative bioincompatibility. Allergoid reactions and disturbances of the hemostatic system represent the main fields of biological investigations. Due to the extent of clinical and experimental works the ubiquitous interactions between these molecules and cellular and/or protein systems have emerged. The development of a new family of low osmolality ionic or non-ionic contrast molecules had decreased the incidence of minor reactions, but did not modify the frequency of severe accidents and even led to the emergence of new iatrogenic syndromes. Despite extensive laboratory investigations there are still no predictive criteria nor any specific therapeutic prevention of these allergoid reactions. The suggested future line of investigation concerns the physicochemical interaction of CM and targeted biological systems which may allow the analysis and predictivity of these interactions at the molecular level.