Allergic skin diseases include urticarial, angioedema, contact dermatitis, and atopic dermatitis, but atopic dermatitis (AD) best represents the systemic idea of allergy. In this article, we examine the off-label and beyond-label usage of approved medications, experimental therapies in development, and interesting new targets. Recent reports of the effective use of therapies for skin allergies and prospective targets for the development of innovative treatments were looked for in MEDLINE. In addition, we searched ClinicalTrials.gov for current and recent randomized clinical studies on skin allergies. Accordingly, relevant articles were selected and reviewed. In Conclusion, innovative and superior therapies for skin allergies are urgently required. Several medicines are now in clinical trials, and other ones should be developed to exploit the numerous interesting targets recently discovered and described. Mas-related G protein-coupled receptor X2, the histamine4 receptor, C5a and its receptor, inhibitory mast cell receptors other than Siglec-8, interleukin 33, interleukin 25, thymic stromal lymphopoietin, and stem cell factor are all possible targets for future therapies.