Recently, dermatologists have witnessed a revolution in our therapeutic armamentarium with the development of several novel biologic immunomodulators. Although psoriasis remains the only condition in dermatology for which the use of biologic immunomodulators has been approved by the Food and Drug Administration, these drugs have the potential to significantly impact the treatment of several inflammatory conditions in dermatology. This article includes a review of the mechanism of action, dosing, and side-effect profile, as well as a review of the current literature on off-label uses of the CD20-positive B-cell antagonist rituximab, the IgE antagonist omalizumab, the tumor necrosis factor-⍺ antagonists infliximab, etanercept, and adalimumab, and the T-cell response modifiers efalizumab and alefacept.