As our understanding of connective tissue disease expands, so too does our therapeutic armamentarium. We have learned that autoimmunity triggers inflammation through unchecked, proliferative cell-mediated inflammation. By targeting this arm of the cytokine cascade, it may be possible to arrest further progression. Several biologic agents, such as etanercept, alefacept, infliximab, efaluzimab, and, recently, adalimumab, have come to market for adult psoriasis and are now undergoing trials for juvenile SLE, psoriasis, and psoriatic arthritis. Of note, etanercept has been used successfully in juvenile rheumatoid arthritis for more than 10 years. These agents target cell-mediated inflammation through various mechanisms and hold great promise for the treatment of many of the disease states discussed above. Moreover, the biologics carry an improved side-effect profile not seen with traditional agents such as corticosteroids and will be central in the evolution of targeted therapeutics for these complex immunologic diseases.