The skin is one of the largest immunologic organs and is affected by both external and internal factors, as well as innate and adaptive immune responses. Many skin disorders, such as atopic dermatitis, contact dermatitis, urticaria, angioedema, psoriasis, and autoimmune blistering disorders, are immune mediated. Most of these diseases are chronic, inflammatory, and proliferative, in which both genetic and environmental factors play important roles. These immunologic mechanisms might have implications for potential targets of future therapeutic interventions.