The clinical laboratory has a well defined role to play in the diagnosis and management of patients with allergy. Elevated serum levels of total IgE and/or allergen-specific IgE indicate that an IgE mediated event has occurred. Methods such as basophil degranulation and basophil or leukocyte histamine release can provide similar information. Sensitive and precise methods suitable for automation are available for quantitation of histamine in whole blood or plasma. Methyl histamine can be assayed in urine. Eosinophil cationic protein levels in serum can be used as an indicator of eosinophil activation in disorders such as asthma and atopic dermatitis. Similarly, serum mast cell tryptase levels can confirm or exclude an anaphylactic reaction both in life and as a cause of death. This review documents and compares commercially available methods for these assays and discusses their application to screening, diagnosis, and management of patients with allergy.