Proper diagnosis of adverse drug reactions, although often complicated and difficult, is important for the patient and the physician. Often the question of whether it is safe to readminister a medication is an important clinical judgment that needs to be made. Alternative medications may be less effective or have greater toxicities or cost, or both. Areas of ongoing research to improve diagnostic precision for allergic drug reactions include further understanding of the immunochemistry of allergenic medications, improvement of the reproducibility and sensitivity of relevant in vitro assays, and further validation of computer-assisted evaluation of adverse drug events. The positive and negative predictive values for these diagnostic tests need to be better defined whenever possible. At present, the primary diagnostic tool for properly assessing immunologic drug reactions remains a meticulous and detailed history obtained by an astute, knowledgeable, and motivated physician.