Oral drug reactions have many clinical manifestations and are produced by numerous medications. These reactions may be the result of an allergic reaction to systemically administered drugs or as an indirect effect of the action of the drug on other tissues. Other oral drug reactions may be the result of local or topical medications. These reactions are either a result of an allergic, delayed-type hypersensitivity, or a local primary irritation. The appearance may be nonspecific or it may resemble several distinct clinical entities. The diagnosis of these oral drug reactions is made with a good clinical history and examination, along with a high index of suspicion. Often there are multiple factors involved that complicate the clinical picture. The clinician who is familiar with the types of oral drug reactions caused by medications, the mechanisms by which these reactions occur, and which medications are most likely to cause the reaction will be prepared to make the correct diagnosis and treatment recommendations.