BACKGROUND Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Safe and effective long-term treatments are needed. Biologic treatments that inhibit the immunopathogenesis of psoriasis have helped meet this need. OBJECTIVE The purpose of this study was to compare the efficacy of biologic therapies used for psoriasis. METHODS A literature search was performed using PubMed and the keywords '(PASI-75 OR efficacy) AND psoriasis AND (adalimumab OR alefacept OR etanercept OR infliximab OR ustekinumab).' Randomized, double-blind, and placebo-controlled studies on US FDA-approved biologics were selected. Studies assessing the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index (PASI-75) within a 12-week period were included. Studies on pediatric populations and psoriatic arthritis were excluded. The weighted average of PASI-75 for each reported regimen was calculated to determine the efficacy of biologic agents used for moderate-to-severe psoriasis. Tolerance and secondary efficacy measures were also examined for the selected studies. RESULTS FDA-approved regimens of adalimumab, infliximab, ustekinumab, and alefacept were effective in treating moderate-to-severe psoriasis. Weighted average PASI-75 scores for infliximab, ustekinumab, adalimumab, etanercept, and alefacept were 78.6%, 72.1%, 70.5%, 48.1%, and 21%, respectively. CONCLUSIONS The comparative efficacy of biologic agents data was limited to 12 weeks, thus generalizing the results to longer treatment periods may not be accurate. CONCLUSIONS Various biologic agents for psoriasis were effective at 12 weeks in placebo-controlled trials. Available data cannot fully account for situations in clinical practice, in which combination and longer duration of therapy may be required. When choosing the most effective or best agent, multiple factors should be considered including patient preference, cost, tolerance, adverse effects, dosing schedule, and mode of administration.