Over the last two decades, research developments have revolutionized our understanding of the pathogenesis of psoriasis and of the contribution of several cytokines in the manifestation of the disease. The key role of TNF-α in the pathogenesis of psoriasis has been extensively studied and its therapeutic action, initially observed in experimental models, has been clinically translated into therapeutic agents with remarkable efficacy in the treatment of the disease. There are currently two classes of marketed biologic drugs that reduce TNF-α bioavailability and are used clinically in psoriasis: the soluble TNF-α receptor-Fc fusion protein (etanercept) and the anti-TNF-α monoclonal antibodies (adalimumab and infliximab). The present article reviews the pharmacodynamic properties of the three TNF-α inhibitors and discusses possible differences in their mode of action, clinical efficacy and safety profile.