With the completion of several phase 2 and phase 3 clinical studies, the efficacy and tolerability of alefacept in patients with chronic plaque psoriasis is now well studied. The majority of patients treated with a single course of intravenous or intramuscular alefacept experienced a clinically meaningful response. The efficacy of alefacept correlated with its ability to selectively target and reduce the number of pathogenic memory T cells. A second course of alefacept resulted in further clinical improvement, with increasing response rates and prolonged response duration following treatment cessation. Subpopulation analyses demonstrated that alefacept is effective in a broad spectrum of patients with psoriasis, regardless of disease severity, history of and response to prior antipsoriatic treatment, or whether patients are refractory to or have contraindications to other systemic psoriasis therapies or phototherapy.