Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health. This review aimed at exploring the phenomena of chemical-induced contact allergy starting from a mechanistic understanding, immunoregulatory mechanisms, passing through the potency of contract allergen until the hazard identification, pointing out the in vitro models for assessing contact allergen-induced cell activation and the risk prevention.