Management of psoriasis over the last decade has changed significantly with the introduction of biological therapies. Ustekinumab is a first-in-class biological agent, inhibiting the action of IL-12 and IL-23, and has provided further evidence for the role of Th1 and Th17 lymphocytes in the pathogenesis of psoriasis. Efficacy has been clearly demonstrated in three Phase III clinical trials. Week 12 Psoriasis Area and Severity Index (PASI) 75 was observed in 66.4-75.7% of patients with PASI 90 achieved in 36.7-50.9%. This marked clinical response is also reflected in a significant improvement in quality of life. The most recent Phase III clinical trial has demonstrated the superior efficacy of ustekinumab (regardless of dosing regimen) compared with high-dose etanercept at week 12. Long-term efficacy has been demonstrated over 148 weeks with 64-76% of patients maintaining PASI 75. The role of ustekinumab in the treatment of psoriatic arthritis has shown some benefit in Phase II clinical trials. Phase III clinical trials are pending and will provide further guidance on management of concurrent disease. The currently available safety data are on the whole reassuring, although ongoing vigilance remains central to the detection of rare or late sequelae.