Background Alefacept was the first biologic agent approved in the United States for the treatment of moderate to severe chronic plaque psoriasis (January 2003). Standard prescription is 12 weekly intramuscular doses. The mechanism of action involves the inhibition of T-cell activation and the selective induction of apoptosis of memory T cells. A proportion of patients responding to therapy have been reported to experience remissions of approximately 7 to 8 months, characterized by disease-free and treatment-free intervals. Objective We sought to evaluate the efficacy and safety of alefacept treatment in patients with psoriasis during routine clinical practice. Methods We conducted a retrospective chart analysis of data involving 201 patients and 296 courses of alefacept from February 2003 to January 2006. Standard informed consent was obtained. Results Of the 62 patients (32.6%) who achieved an excellent response, 45% received dosage regimens defined as alternative and 73% had concomitant therapy in at least one of the treatment courses that they received. The average remission time of these patients who achieved an excellent response was approximately 7 months, with a maximum of up to 25 months. Adverse events were generally manageable and rarely led to treatment discontinuation. Limitations Study data rely on retrospective analysis of chart-documented clinical examination findings, and patient compliance with visit schedules. Conclusion Alefacept is a long-term treatment option for psoriasis with long-term remissions noted in a proportion of patients.