Several systemic drugs are available for the treatment of moderate-to-severe plaque psoriasis, including photochemotherapy, retinoids, cyclosporin, methotrexate, and fumarates. Although these options have been shown to maintain efficacy, frequently they produce significant subjective side effects. Recently, there has been a significant advance in developing newer medications that may be used for psoriasis. The progress in laboratory techniques has improved our understanding of the immuno-pathogenesis of psoriasis to a point where a number of key cytokines and immune cells - notably tumor necrosis factor-alpha (TNF-α) and T-cells respectively have been identified as critical factors contributing to the immuno-pathogenesis of the disease. Many of these medications are termed "biologic response modifiers" or, more commonly, "biologicals". The latter are a set of different engineered proteins designed to modify defined patho-physiological pathways that regulate pivotal immunological processes such as lymphocytes activation and cytokines production. New strategies and new formulation of biologic therapies, angiogenesis inhibition, immunomodulatory compounds, intracellular messenger targets, are of current interest to dermatologists and medicinal chemists. This review summarizes the current understanding of the immuno-pathogenesis of psoriasis, the mechanism of action and efficacy of current biologic therapies, new patents and their possible future applications in the treatment of psoriasis.