Psoriasis is a common chronic inflammatory disease of the skin that has a significant impact on quality of life. A small number of systemic therapies are well established in psoriasis management. These have immunosuppressive and/or anti-proliferative effects on the skin and immune system. As understanding of the pathogenesis of psoriasis has advanced over the last 2 decades, there has been clearer appreciation of the genetic, cellular and immunological components of disease expression, which has provided new insight into potential therapeutic targets, including the development of biological therapies. Biologics offer a unique opportunity to block or inhibit specific key components of psoriasis pathogenesis. The introduction of tumour necrosis factor (TNF).α and interleukin (IL)-12/-23 inhibitors has resulted in remarkable clinical responses in patients with severe psoriasis and has led to the development of a range of other cytokine modulators currently undergoing investigation. More recently, research in keratinocyte biology and immune cell function, particularly intracellular signalling, has afforded additional opportunities to develop a range of small-molecule oral preparations that may prove effective in disease control. This paper reviews current and emerging systemic treatments in the management of psoriasis.