Clinical laboratory analyses aid in the diagnosis and management of human allergic (IgE-dependent) diseases. Diagnosis of immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once symptoms compatible with an allergic disorder have been identified, a skin test, blood test, or both for allergen-specific IgE antibodies provide confirmation of sensitization, which strengthens the diagnosis. Skin testing provides a biologically relevant immediate-type hypersensitivity response with resultant wheal-and-flare reactions within 15 minutes of allergen application. Allergen-specific IgE antibody in serum is quantified by using 3 laboratory-based autoanalyzers (ImmunoCAP, Immulite, and HYTEC-288) and novel microarray and lateral-flow immunoassays. Technologic advances in serologic allergen-specific IgE measurements have involved increased automation, with enhanced reproducibility, greater quantification, lower analytic sensitivity, and component-supplemented extract-based allergen use. In vivo provocation tests involving inhalation, ingestion, or injection of allergens serve to clarify discordant history and skin- or blood-based measures of sensitization. Other diagnostic allergy laboratory analyses include total and free serum IgE measurement, precipitating IgG antibodies specific for organic dusts, mast cell tryptase, and indicator allergen analyses to assess indoor environments to promote patient-targeted allergen avoidance programs. A critique is provided on the predictive utility of serologic measures of specific IgE for food allergy and asthma. Reasons for the lack of clinical utility for food-specific IgG/IgG4 measurements in allergy diagnosis are examined. When the specific IgE measures are inconsistent with the clinical history, they should be confirmed by means of repeat and alternative method analysis. Ultimately, the patient's clinical history remains the principal arbiter that determines the final diagnosis of allergic disease.