The use of topical immunomodulators in pediatric patients is an important topic in the clinical practice. Their prescription for chronic diseases suggests the necessity of evaluating their efficacy and safety profile in a long term period. In children they can develop systemic adverse events after their application, though sometimes they are useful to reduce the long consumption of other drugs, as topical steroids, or to have influence in the critical aspects of immunomodulation. Pimecrolimus and tacrolimus are two topical calcineurin inhibitors, from which there are several reports that support their efficacy in pediatric patients with atopic dermatitis. Recently, the FDA issued a recommendation for their topical use in a sporadic way in two years old children or older that have moderate to serious atopic dermatitis and that have not responded to other treatments. This article shows the results of several studies in which these drugs have been applied for a long time in children with atopic dermatitis. The more frequent adverse effects were: infections, pyrexia, burning, pruritus, erythema, and papules in the application area. In suckling babies they were: dry skin, pruritus, infections, constipation, erythema, and papules. Even when these adverse effects have been reported with relative frequency, their controlled use in concrete clinical conditions is still a therapeutic option and they should be considered particularly useful in the treatment of atopic dermatitis without positive reaction to other treatments in children older than two years, during short periods and in cases in which immunocompromised situations have been ruled out.