Background: Large-scale clinical trials provide clear evidence of the efficacy and short-term toxicity of biologic therapies for psoriasis. However, to date, there are few reports of the practical use of these therapies outside of the trial setting and, to our knowledge, none from a U.K. cohort of patients with psoriasis. Objectives: (i) To assess efficacy and safety of efalizumab, etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21.8 and 21.7, respectively, outside of the clinical trial setting. (ii) To examine our approach to the processes involved in the initiation of biologic therapies in the era of National Institute for Health and Clinical Excellence guidance. Methods: A retrospective case-note review to identify all patients initiated on biologic therapies for psoriasis in a U.K. tertiary referral centre. Results At 3 months of treatment the efficacy of efalizumab (n = 28), etanercept (n = 70) and infliximab (n = 20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35% and 85%, respectively. All three biologics used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biologic therapy in 30% of cases. Streamlined approaches to screening and funding significantly (P ≤ 0.05) hastened the initiation of biologic therapies. Conclusions: In a cohort of U.K. patients with severe psoriasis, biologic therapies have proved to be a significant step forward in expanding the therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long-term safety of such drugs. © 2008 The Authors.