Imiquimod is used topically in the treatment of numerous dermatologic conditions. Imiquimod modifies the immune response through cytokine induction of the T-cell helper subset, correlating with the expression of interferon alpha, tumor necrosis factor alpha, interferon gamma, and interleukins (ILs) 1 and 12. Reciprocal inhibition of TH2 immune response occurs via up-regulation of interferon gamma and down-regulation of TH2-associated cytokines, including IL-4, IL-5, IL-6, IL-10, and IL-13. Alopecia universalis is a severe form of alopecia thought to arise from T-cell mediated autoimmune disease of the hair follicle. There have been no case reports noting a beneficial effect of topical imiquimod in the treatment of alopecia universalis. We present a case of a 15-year-old adolescent girl with alopecia universalis since age 8 who experienced transient hair growth after topical application of imiquimod.