Urticaria (i.e., pruritic, raised wheals) and angioedema (i.e., deep mucocutaneous swelling) occur in up to 25 percent of the U.S. population. Vasoactive mediators released from mast cells and basophils produce the classic wheal and flare reaction. Diagnosis can be challenging, especially if symptoms are chronic or minimally responsive to therapy. A thorough medical history, physical examination, and methodical investigation are necessary to uncover diagnostic clues. Although serious medical illness can occur concurrently with chronic urticaria, acute urticaria generally is benign and self-limited. The mainstay of therapy for urticaria is avoidance of known triggering agents, judicious use of oral corticosteroids, and treatment with long-acting second-generation antihistamines, H2-receptor antagonists, tricyclic antidepressants, and anti-inflammatory leukotriene antagonists. Consultation for investigative therapy may be necessary if symptoms continue despite a stepwise approach to diagnosis and therapy.