Alefacept is a fully human fusion protein, being the first biologic agent approved for the treatment of chronic, moderate to severe plaque-type psoriasis. Its dual mechanism of action involves inhibition of T-cell activation and selective reduction of memory T cells. It has a slow onset of action, peaking approximately 18 weeks after the first injection. However, it is associated with long remissions without the need for maintenance therapy in psoriatic patients and its efficacy improves with subsequent courses with a high safety profile. The mechanism of action, the results of the clinical trials, its efficacy, pharmacodynamic effects on circulating lymphocytes, and safety and tolerability of alefacept are summarized in this review. Current treatment guidelines are also presented.