IMPORTANCE Alopecia universalis is an uncommon form of alopecia areata (AA) involving hair loss over the entire scalp and body and is often difficult to treat. Tumor necrosis factor (TNF)inhibitors have been largely unsuccessful in treating AA and have been reported to induce or worsen AA in patients.We report herein a case of alopecia universalis successfully treated with adalimumab and discuss the possible mechanism.OBSERVATIONS A woman in her 30s with alopecia universalis, refractory to multiple treatment modalities, was successfully treated with adalimumab.CONCLUSIONS AND RELEVANCE Tumor necrosis factor has multiple important roles in the pathogenesis of AA, and its interplay with other cytokines, specifically interferons, may be responsible for the development of AA in patients treated with TNF inhibitors.Pharmacogenetics and the inherent physiologic levels of TNF may explain why TNF inhibitors cause AA in some individuals, while treating AA in others. These conclusions warrant further investigation on this subject.