Pimecrolimus is an ascomycin macrolactam derivative with anti-inflammatory and immunomodulatory activity that belongs to the class of calcineurin inhibitors. It was developed after the attempt to discover alternatives to corticosteroids for the treatment of inflammatory skin diseases. Although pimecrolimus has been only approved for the treatment of atopic dermatitis, many clinical reports have proved its efficacy in a variety of skin conditions. However, corticosteroids remain the treatment of choice in inflammatory skin diseases. The possibility that pimecrolimus deserves a greater role in the long-term treatment of skin diseases is discussed herein by reviewing the published clinical studies that compare pimecrolimus and corticosteroids.