Etanercept has demonstrated excellent safety and efficacy in the treatment of patients with psoriatic arthritis (PsA), which is a chronic inflammatory arthritis. Composed of 2 soluble TNF receptor (p75) domains fused to human immunoglobulin, etanercept neutralizes the inflammatory cytokines TNF and lymphotoxin-alpha. In a phase 2, randomized, placebo-controlled trial of 60 patients with PsA, etanercept 25 mg subcutaneously twice weekly resulted in significantly more improvement in arthritis and skin symptoms than placebo. At 12 weeks, 87% of etanercept-treated patients achieved a clinical response by the Psoriatic Arthritis Response Criteria compared with 23% of the placebo group. The percent of those patients achieving an American College of Rheumatology 20% (ACR20), ACR 50, and ACR70 response were 73%, 50% and 13%, respectively, compared to 13%, 3%, and 0% in the placebo group. The median improvement in skin disease activity (assessed by the Psoriasis Area and Severity Index) in the etanercept group was 46% versus 9% in the placebo group. In a 6-month open-label extension of this study, patients who originally had received placebo rapidly achieved responses to etanercept that were comparable to responses in the group originally randomized to the active drug; in the group originally on etanercept, efficacy was maintained, and a large proportion of patients decreased or discontinued concomitant prednisone or methotrexate. Etanercept was generally well tolerated throughout this trial. A phase 3 trial confirmed the efficacy and safety of etanercept in PsA, with 59% of etanercept-treated patients meeting the ACR20 improvement criteria at 12 weeks compared with 15% of placebo-treated patients. Significant improvements in skin lesions relative to placebo were also observed No adverse events were significantly more common with etanercept than with placebo. Several case studies add to our body of knowledge of etanercept in PsA. Etanercept is well suited to long-term therapy and provides a valuable treatment option for PsA.