Evidence is accumulating that supports a role for acute desensitization for IgE-mediated drug allergy in those patients for whom no alternative drug exists. While most of the studies have been performed in penicillin-allergic patients, this procedure has been used safely in patients with IgE sensitivity to other agents. In addition, it has been shown that modified desensitization protocols may be effective in the prevention of other immune-mediated drug reactions, as well. Thus, while much research remains to be done in this area, drug desensitization will continue to be a powerful tool in the management of drug allergy.