Hypersensitivity reactions to contrast media (CM) are frequent causes of anaphylactically induced fatalities. Adverse events after CM exposure are classified into immediate and non-immediate reactions, with differing pathomechanisms. In the majority of patients with immediate reactions, IgE-mediated allergy can not be demonstrated and the underlying mechanism remains unknown. However, recent data has provided evidence for skin test positivity and/or specific IgE in some patients with severe reactions. Cell-mediated hypersensitivity is the responsible mechanism for the majority of non-immediate skin eruptions. Skin tests have been employed to confirm this hypersensitivity. Previous reactors have an increased risk to develop new reactions upon repeated exposure, however, other risk factors are poorly defined. The use of skin tests for the selection of a "safe" CM is controversially discussed; information on sensitivity and specificity is lacking. New in-vitro assays have to be developed and/or validated. Premedication of previous reactors is common practice among radiologists, however, its precise role in the prevention of severe CM reactions to lower-osmolality CM has not been demonstrated. Thus, the main future tasks are to develop and validate allergic tests procedures, which may identify patients at risk and/or may confirm CM tolerance, and to reassess the value of different premedications in the prevention of hypersensitivity reactions.