There are several well-established guidelines for the treatment of psoriasis. Guidelines have been proposed in the United States by the American Academy of Dermatology (AAD), in Europe by the European S3, in the United Kingdom by the National Institute for Health and Care Excellence (NICE), and in Canada by the Canadian Dermatology Association. These guidelines are predominantly evidence-based, supported by expert panel consensus where evidence is lacking. Cyclosporine, a potent calcineurin inhibitor that acts selectively on T-cells, revolutionized the world of immunosuppression upon its discovery in 1970. Since its approval in 1997 by the U.S. Food and Drug Administration for the treatment of psoriasis, cyclosporine has been used with great efficacy in the treatment of not only psoriasis but also a wide consortium of dermatological diseases. However, in the past decade or so, many dermatologists have become increasingly hesitant to use this important drug because of its potent toxicity profile. The purpose of this article is to review and compare the current evidence-based guideline recommendations for the use of cyclosporine in the treatment of psoriasis. Although the various guidelines are similar in their initial treatment recommendations, significant differences exist in recommendations on maximal treatment duration (1 year versus 2 years), intermittent short-term versus continuous therapy, use in erythrodermic and palmoplantar psoriasis, as well as recommendations on managing cyclosporine-associated side effects. By following guideline recommendations, cyclosporine remains an excellent and indispensable tool for the dermatologist treating moderate-to-severe psoriasis.