Allergy skin testing is a diagnostic tool used to detect specific IgE-mediated allergic responses by inducing a wheal and flare reaction. This reaction occurs due to mast cell degranulation upon allergen exposure, with histamine and tryptase released within minutes and peaking at 30 minutes. The primary methods for in vivo testing include skin prick testing (SPT) and intradermal dilutional testing. SPT is a commonly used technique with high sensitivity (85–87%) and specificity (79–86%) for allergic rhinitis and asthma. It is typically performed on the forearm or back, with the upper or lower back providing more accurate results. SPT offers rapid results, relative safety, and clear identification of sensitization, though it has limitations in negative predictive value. Intradermal dilutional testing is preferred when higher sensitivity is needed. Skin testing should be guided by a patient’s history and suspected atopic disease. However, several medications, including antihistamines, beta-blockers, tricyclic antidepressants, and certain antipsychotics, can interfere with test accuracy and should be discontinued for varying durations before testing. Additionally, dermatographism, uncontrolled asthma, and extensive atopic dermatitis may contraindicate testing, necessitating alternative diagnostic approaches. Proper clinical preparation for allergy testing includes maintaining appropriate storage conditions for allergen extracts, ensuring a well-equipped testing environment, and having emergency anaphylaxis management supplies available. Physicians must directly supervise testing to manage potential systemic reactions. Environmental and biological factors such as seasonal variations, cross-reactivity between food and aeroallergens, and age-related differences in skin reactivity can influence test outcomes. Ultimately, allergy skin testing provides valuable diagnostic insights but must be interpreted alongside clinical symptoms to confirm allergic disease.