During the past several years, one of the major focuses in psoriasis research has been the development of novel biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention, with the hope that such specificity will result in fewer side effects than traditional therapies. In this 2-part review, we present an update on the progress of the 4 biologic agents that most likely will be the first available for clinical use: infliximab, etanercept, efalizumab, and alefacept. The structure and mechanism of each drug will be reviewed, as well as the most recent clinical experience and safety data. The first article of this review will focus on the therapies that inhibit tumor necrosis factor α (TNF-α).