The primary treatment of urticaria involves identification and discontinuation of the offending agent. Addition of an antihistaminic agent may then be necessary to control pruritus. Because of variable response rates between patients, several alternative agents may need to be tried before the most effective regimen is found. Based on the studies reviewed here, it appears that low-dose doxepin (10 mg po tid) is a potentially effective and well-tolerated alternative in patients who do not respond to conventional antihistamines. This success may be in part due to the more potent H1- and H2-blocking properties associated with doxepin. Data regarding the topical use of doxepin are less convincing; however, the drug appears to have some clinical use for the short-term treatment of pruritus. Doxepin cream does not appear to be as effective as systemic therapy, and adverse effects (including sedation) and drug interactions are still problematic. Topical use may be best suited to conditions involving intact skin that do not require application to large areas of the body, thereby reducing systemic absorption and adverse effects.