Systemic drugs are used in the treatment of several skin diseases. In order to obtain best therapeutic results and prevent side effects, the patients should be carefully screened before and thoroughly evaluated during treatment. In this article guidelines for selection and follow up of patients receiving systemic drugs for their skin diseases are presented. These drugs include azathioprine, anti-malarials, spironolactone, PUVA, dapson, retinoids, cyclosporin, cyclophosphamide, gold, colchicine, corticosteroids, and methotrexate.