Psoriasis is a complex systemic immune inflammatory disease whose burden of disease includes poorer quality of life, a high prevalence of serious comorbidities, and a potentially decreased life span-hence the continued need to search for new treatment options. ABT-874 (Abbott Laboratories, Saint-Laurent, QC,) and ustekinumab (CNTO 1275, Ortho Biotech, Toronto, ON) are two monoclonal antibodies against interleukins 12 and 23 (IL-12/23), key mediators of T-cell differentiation in the pathogenesis of psoriasis. The results of a 12-week, phase II, dose-finding study of ABT-874 have been encouraging. More recently, level 1 evidence has emerged for ustekinumab in two placebo-controlled phase III trials, PHOENIX 1 and PHOENIX 2; therapeutic responses to ustekinumab have been maintained up to 76 weeks of follow-up, and quality of life has significantly improved with ustekinumab. Both agents produced few and mild adverse events, and the rates of serious infections and cancers were very low and similar to those of placebo. These promising results strongly confirm the central role of IL-12/23 in psoriasis and its importance as a therapeutic target.