The array of systemic medications used in the treatment of psoriasis is rapidly expanding. In the United States, methotrexate, retinoids, and cyclosporine are the only systemic drugs approved by the Food and Drug Administration for the treatment of psoriasis. Monitoring and dosage recommendations for these medications are reviewed. Other drugs that are currently available include tacrolimus, mycophenolate mofetil, hydroxyurea, 6-thioguanine, and sulfasalazine. Experience with these drugs is summarized, and dosage and monitoring recommendations in published literature are presented. Combinations of different treatments are addressed and investigational therapies that are in development are reviewed. (J Am Acad Dermatol 2001;45:649-61.) Learning objective: At the conclusion of this learning activity, participants should be familiar with various systemic treatments for psoriasis, including combinations of therapies. Participants should also have more knowledge of dosage and monitoring recommendations of drugs used for psoriasis and be more aware of possible drug interactions and their side effects.