Alefacept is a novel biologic agent for the treatment of plaque psoriasis. Alefacept is a fully human recombinant dimeric fusion protein composed of the terminal portion of Leukocyte Functioning Antigen-3 (LFA-3) and the Fc portion of human IgG(1). The drug likely works in part by inducing the apoptosis of memory effector (activated) T cells that play a central role in the pathophysiology of psoriasis. Alefacept also may interrupt the direct immunologic activation of T cells by antigen presenting cells. Alefacept is administered as a course of 12 intramuscular injections, but other dosing strategies have been explored. After a course of therapy, statistically more patients receiving alefacept achieve a psoriasis area and severity index (PASI) 75 response than those receiving a placebo. Some patients who achieve PASI 75 also experience long-term remissions from psoriasis. The drug is well-tolerated and adverse events are rare. Off-label use of the drug is growing and may be formally explored in the future.