Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy or immunosuppressive agents have been the first line of treatment for patients with severe psoriasis; however, the long-term use of these agents is limited by dose-dependent toxicities. Alefacept was the first biological agent approved in both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selectively reduces memory T cells. The efficacy and safety of up to two courses of alefacept have been demonstrated in clinical trials, and thus, this review focuses on new data to optimise the use of this biological agent. Emerging data indicates that multiple courses of alefacept for the long-term treatment of psoriasis are safe and effective. In addition, data are reviewed on the use of alefacept in combination with other agents and in other diseases, including psoriatic arthritis.