IgE, one of the five subclasses of antibodies found in mammals is a key molecule in allergy responses and inflammation. When an individual is exposed to an allergen, the allergen particles bind to the sensitized mast cells bound to IgE. Mast cells secrete components of allergic reactions such as cytokines, histamines, etc. Hence a person undergoing persistent or periodic symptoms of allergy can be advised to be tested for total IgE levels. This test is also recommended when the allergen is unknown and its detection is required for effective immunotherapy/ allergen shots against specific allergies. Quantitative measurement of serum IgE with other clinical indicators can provide useful information for the differential diagnosis of Atopic and Non-Atopic diseases. For diagnostic purposes, results should always be assessed with the patient’s medical history, clinical examination, and other findings.