Psoriasis is a chronic skin disorder that affects approximately 2% of the population of the US and Europe. Over the past several years, one of the major focuses of psoriasis research has been developing biological therapies that can be used to treat this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to provide an update on the development of the tumor necrosis factor-α inhibitors that are available or under investigation for clinical use in psoriasis. These inhibitors are infliximab, etanercept, and adalimumab, as well as the T cell-targeted therapies efalizumab and alefacept. In addition, the article will discuss ustekinumab, which is a fully human immunoglobulin G1 monoclonal antibody directed against the p40 subunit of interleukin-12 (IL-12) and IL-23 that is currently under consideration by the US Food and Drug Administration and approved in other countries.Adv Psor Inflam Skin Dis 2009;1(1):15–20.