Innovations in biotechnology have made possible the development of several new systemic therapies for psoriasis - the "biologicals", a new group of compounds including monoclonal antibodies, fusion proteins and recombinant proteins. These novel biotechnological advances potentially offer designer drugs, which interfere with specific targets in the pathophysiological network of psoriasis and are thus much safer. The therapeutic strategy of biologicals is based on the knowledge derived from pathogenetic studies, which have focused on targeting disease relevant T-cell- or mediatorsystems. Important targets include inactivation of soluble mediators such as tumor-necrosis-factor-α, the blockade of receptors for cytokines, adhesion molecules and the interference with T-cell activation by antigen-presenting cells. In addition, recombinant cytokines are able to modulate the immunological balance of this chronic inflammatory skin disease. Currently, up to forty agents are under investigation for the treatment of psoriasis. Four of these agents, alefacept, efalizumab, etanercept and infliximab have already impacted on routine clinical practice. Current developments in the treatment of psoriasis with biologicals are reviewed.