Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Several lines of evidence have demonstrated the correlation between elevated levels of TNF and psoriasis, suggesting that interfering with the inflammatory effects of TNF may help resolve psoriatic lesions. The biological agent, etanercept, is a fully human soluble TNF-receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, and psoriatic arthritis. In several well-controlled clinical trials, etanercept showed sustained efficacy in reducing the signs and symptoms of psoriasis in patients with moderate-to-severe disease. With the exception of injection site reactions, adverse event rates were similar to placebo and did not increase across higher doses. No opportunistic infections, including tuberculosis, were reported. From analysis of the available clinical trials, etanercept appears to be an effective and well-tolerated agent for the treatment of moderate-to-severe psoriasis.