TNF-a inhibitors, which include adalimumab, infliximab, etanercept, certolizumab, and golimumab, and IL-12/23 inhibitor, ustekinumab, have been widely used as a U.S. Food and Drug Administration (FDA) approved for the treatment of psoriasis. Outside of psoriasis, high levels of TNF-a had also been found in several skin diseases including hidradenitis suppurativa. IL-12 and IL-23 play important role in the pathogenesis of SLE, alopecia areata, and vitiligo. This paper reviews the off-label uses of TNF-a inhibitors and IL-12/23 inhibitors in skin disorders.