Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis with a prevalence of 7-21% in school-aged children. Childhood AD has a profound impact on the social, personal, emotional, and financial perspectives of families. For the last half-century, topical corticosteroids of different potencies have been the mainstay of topical therapy. In recent years, two topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, have become available for the treatment of AD. Both tacrolimus and pimecrolimus have been extensively evaluated in the management of pediatric AD. Trials comparing them with placebo, topical corticosteroids, and each other have shown them to be effective and safe for continuous short-term use, and for noncontinuous use for up to 4 years. Long-term safety of TCIs is not known as they have been in clinical use for less than a decade.