Allergies to various antibiotics are reported by a substantial proportion of patients. As a result, clinical decision support programming generates frequent warnings when prescribing within electronic medical records. For a variety of reasons, the majority of these warnings may be inappropriate. Our improved understanding of the underlying physiology of allergic processes reveals that the majority of cross-reacting antibiotic allergies are implausible. Appropriate history taking and workup can invalidate many more warnings. Electronic medical records ideally should permit documentation that would facilitate more accurate entry and eliminate similar future warnings.