Psoriatic arthritis (PsA) is a chronic inflammatory arthritis and considered to be a less severe condition than rheumatoid arthritis. PsA patients have been treated for a long time with a number of different agents, from non-steroidal anti-inflammatory drugs to one or more disease-modifying antirheumatic drugs. In the last decade, recognition of the central role of tumor necrosis factor-alpha (TNFα) in the immunopathogenesis of many rheumatic diseases, including PsA, has led to the development of TNFα blockers. In PsA, these agents are uniquely efficacious in the treatment of different patterns of the disease, as well as slowing progression of erosive damage in the peripheral joints. However, a significant number of patients withdraw from therapy because of failure or poor tolerability. Among the novel therapeutic targets, interleukin (IL)-23/IL-12 has been investigated for the treatment of chronic inflammatory disease. In particular, ustekinumab is a human monoclonal antibody that prevents human IL-12 and IL-23 from binding to the IL-12Rβ1 receptor chain of IL-12 (IL-12Rβ1/β2) and IL-23 (IL-12Rβ1/23R) receptor complexes on the surface of natural killer cells and T-cells. Ustekinumab has been approved only for treatment of chronic plaque psoriasis, but also represents an interesting agent for treatment of PsA. © 2014 Montepaone et al.