There is a high medical need for better therapies for psoriasis. Based on new insight into the pathophysiology of this frequent immune disease, a number of novel systemic immunomodulatory therapies are currently in clinical development. These include approaches targeting antigen presentation and costimulation, T cell activation and leukocyte adhesion, action of proinflammatory mediators, and modulating the cytokine balance. Although mainly only preliminary data are available so far, these trials contribute to a further understanding of the disease and will eventually lead to new therapeutic options for psoriasis. Moreover, since psoriasis can be considered as a visible model disease for T cell-mediated disorders characterized by a type 1 cytokine pattern in general, such approaches may have impact for other immune disorders as well. Here we review the rationale and the initial clinical data of these important recent experimental therapies.