The prospective identification of potential contact allergens and their subsequent safety assessment are pivotal in successful management of this risk to human health. Although much can be learned from the chemical and physical properties of a substance, the definitive information in respect of sensitizing hazard/risk derives from an assessment of the integrated response of the immune system. In recent years, the focus for such assessments has begun to switch from the guinea pig to the mouse, notably to the local lymph node assay (LLNA). In this paper, the current value of the LLNA for hazard identification is reviewed and its regulatory status defined. Once a potential contact allergen has been identified, however, the vital clue to accurate safety evaluation is the assessment of the potency of the allergen. How this can be achieved using the LLNA and employed in safety evaluation is discussed in detail, together with practical suggestions for the deployment of such processes in regulatory toxicology.