Patients with psoriasis typically face longterm therapy for their chronic disease. Often, the therapeutic agents that physicians use to treat them may become less effective or may cause safety or toxicity issues. The clinician must then decide the next therapy for his/her patient and assess benefit/risk of the next therapeutic agent or combination. In moving the patient from one therapy to the next, specific characteristics of the transition must be assessed, and how to stop the existing therapy, and introduce the new agent(s). The decision making process must take into account the longterm risks to the patient. This article focuses on the transition for patients with psoriasis being managed with methotrexate and cyclosporine to retinoids, phototherapy, and newer agents.